Novel Isolated And Purified Strains Of Chikungunya Virus And Polynucleotides And Polypetide Sequences, Diagnostic And Immunogenical Uses Thereof

Abstract

cerns wild-strains of Chikungunya virus isolated from patients exhibiting severe forms of infection and stemming from a human arbovirosis epidemy. The present invention also concerns polypeptide sequences and fragment thereof derived from their genome, the polynucleotide encoding same and their use as diagnostic products, as vaccine and/or as immunogenic compositions.

Description

FIELD OF THE INVENTION

[0001]The present invention concerns wild-strains of Chikungunya virus isolated from patients exhibiting severe forms of infection and stemming from a human arbovirosis epidemy. The present invention also concerns polypeptide sequences and fragment thereof derived from their genome, the polynucleotide encoding same and their use as diagnostic products, as vaccine and/or as immunogenic compositions.

BACKGROUND OF THE INVENTION

[0002]Chikungunya virus (CHIKV) is a mosquito-transmitted Alphavirus belonging to family Togaviridae [1, 2]. It was isolated for the first time from a Tanzanian outbreak in 1952 [3]. It is responsible for an acute infection of abrupt onset, characterized by high fever, arthralgia, myalgia, headache and rash [4, 5]. Polyarthralgia, the pathognomonic sign of the disease, is very painful. Symptoms are generally self-limiting and last 1 to 10 days. However, arthralgia or arthritic symptoms may persist for months or years. In some patients, minor hemorrhagic signs such as epistaxis or gingivorrhagia have also been described.

[0003]CHIKV is geographically distributed in Africa, India and South East Asia. In Africa, the virus is maintained through a sylvatic transmission cycle between wild primates and mosquitoes such as Aedes luteocephalus, Ae. furcifer or Ae. taylori [4]. In Asia, CHIKV is mainly transmitted from human to human by Ae. aegypti and to a lesser extent by Ae. albopictus through an urban transmission cycle. Since the 1952 Tanzania outbreak, CHIKV has caused outbreaks in East Africa (Tanzania, Uganda), in Austral Africa (Zimbabwe, South Africa), in West Africa (Senegal, Nigeria) and in Central Africa (Central African Republic, Democratic Republic of the Congo) [4]. The most recent epidemic re-emergence was documented in 1999-2000 in Kinshasa, where an estimated 50,000 persons were infected [6]. Since the first documented Asian outbreak in 1958 in Bangkok, Thailand, outbreaks have been documented in Thailand, Cambodia, Vietnam, Laos, Myanmar, Malasia, Philippines and Indonesia [4, 5]. The most recent epidemic re-emergence was documented in 2001-2003 in Java after 20 years [7]. Either in Africa or Asia, the re-emergence was unpredictable, with intervals of 7-8 years to 20 years between consecutive epidemics.

[0004]Since the end of 2004, Chikungunya virus (CHIKV) has emerged in the islands of the south-western Indian Ocean. Between January and March 2005, more than 5,000 cases were reported in Comoros. Later in 2005, the virus has circulated in the other islands, i.e Mayotte, Seychelles, Reunion and Mauritius. Starting in December 2005, the rainy season gave rise to a renewed epidemic circulation of the virus. Between Jan. 1 and Mar. 1, 2006, 2,553, 3,471, and 4,650 cases have been reported in Mauritius, Mayotte and Seychelles (Mar. 12, 2006). The most affected island is Reunion with an estimated 212,000 cases until Mar. 12, 2006 (total population: 770,000). More recently, circulation of the virus has been documented in Madagascar.

[0005]In Reunion Island, the first documented cases were patients coming 1 ng back from Comoros in March 2005. More than 3,000 cases were reported from March to June. The transmission was limited during the winter season of the southern hemisphere and a major upsurge has been observed since mid-December, with an estimated 210,000 cases between January and March 2006 [8]. Since March 2005, 85 patients with a confirmed CHIKV infection have developed severe clinical signs (meningoencephalitis or fulminant hepatitis) which justified hospitalization in an intensive care unit. Several cases of meningo-encephalitis and major algic syndrome have been associated with vertical transmission of the virus 9.

[0006]To date, two CHIKV complete nucleotide sequences have been determined, for the strains Ross (accession no: AF490259) and S27 [9], both isolated from patients during the 1952 Tanzania outbreak. Another complete nucleotide sequence has been determined for a strain isolated in Ae. furcifer during the Senegal 1983 outbreak (accession no AY726732). Khan and coworkers [9] showed that the S27 genome was similar in its structure to that of other alphaviruses and that O'nyong-nyong virus (ONN) was the closest relative to CHIKV. In addition, phylogenetic analyses based on partial E1 sequences from African and Asian isolates revealed the existence of three distinct CHIKV phylogroups, one containing all isolates from West Africa, one containing isolates from Asia, and one corresponding to Eastern, Central and Southern African isolates [10]. Strains isolated in 1999-2000 in the Democratic Republic of the Congo belonged to the latter phylogroup [6].

SUMMARY OF THE INVENTION

[0007]An aspect of the invention is to provide new diagnostic and immunologic tools against CHIK virus associated diseases, such as arbovirosis.

[0008]Such an aspect is particularly achieved by providing an isolated and purified wild strain of Chikungunya virus (CHIK) capable of in vitro infecting human cells; and its use for the detection of a CHIKV associated to an arbovirus, or for the preparation of a composition that prevents and/or treats an arbovirus.

[0009]Another aspect of the invention concerns an isolated and purified strain of CHIKV comprising at least one mutation in structural protein E1 and/or structural protein E2; and its use for the detection of a CHIKV associated to an arbovirus, or for the preparation of a composition that prevents and/or treats an arbovirus.

[0010]Another aspect of the invention concerns an isolated and purified polynucleotide comprising all or part of the sequence of SEQ ID NOS: 1, 2, 3, 4, 5 or 6; and its use for the detection of a CHIKV associated to an arbovirus, or for the preparation of a composition that prevents and/or treats an arbovirus.

[0011]Another aspect of the invention concerns a fragment of the polynucleotide of the invention wherein it codes for the ectodomain of glycoprotein E2 or E1; and its use for the detection of a CHIKV associated to an arbovirus, or for the preparation of a composition that prevents and/or treats an arbovirus.

[0012]Other aspects of the invention concern a vector or plasmid comprising a polynucleotide or fragment contemplated by the present invention, and host cell comprising said vector or plasmid; and its use for the detection of a CHIKV associated to an arbovirus, or for the preparation of a composition that prevents and/or treats an arbovirus.

[0013]Yet another aspect of the invention concerns a purified polypeptide encoded by a polynucleotide or fragment of the invention; and its use for the detection of a CHIKV associated to an arbovirus, or for the preparation of a composition that prevents and/or treats an arbovirus.

[0014]A further aspect of the invention concerns a monoclonal or polyclonal antibody or fragment thereof that specifically binds to a polypeptide of the invention; and its use for the detection of a CHIKV associated to an arbovirus, or for the preparation of a composition that prevents and/or treats an arbovirus.

BRIEF DESCRIPTION OF THE FIGURES

[0015]FIG. 1: Localization of the E1 changes on the 3D structure modeled from the crystal structure of SFV E1 [43] [19].

[0016]A) Ribbon diagram of E1, with domain I colored red, domain II yellow and domain III, blue. Green tubes mark the disulfide bonds. The fusion peptide, at the tip of the molecule (in domain II) is colored orange and labeled. The N-terminus and the C-terminus observed in the crystal (which is 30 aa upstream of the transmembrane region) are also labeled. The 2 unique changes observed in the Indian Ocean isolates are indicated by stars and labeled: positions 226 (white) and 284 (magenta).

[0017]B) Partial representation (one octant, slightly extended) of the icosahedral E1 scaffold at the surface of the virion, viewed down a 5-fold symmetry axis. One E1 protomer is highlighted in colors, as in A); all the others are represented in grey. The location of some of the icosahedral symmetry axes are drawn as solid black symbols: pentagon for 5-fold axis, triangle for 3-fold axes, ellipse for 2-fold axes (which in the T=4 lattice of alphaviruses are coincident with quasi 6-fold axes). Open triangles indicate roughly the location of the E2 trimers that interact tightly with E1, covering domain II and the fusion peptide, and presenting the main antigenic sites. The open triangles mark also quasi 3-fold symmetry axes of the T=4 surface icosahedral lattice. A magenta ball marks the location of Glu 284, at an inter-E1 protomer contact site. This contact is propagated 240 times at the surface lattice (note all pink balls drawn on the grey protomers). Note that the fusion peptide, in orange, is pointing up and away from contacts with other E1 protomers. This is more easily seen at the periphery of the virion, where one of them is labeled (FP). In the virion, this region of E1 is not accessible, covered underneath the E2 molecule [19].

[0018]FIG. 2: Phylogenetic relationships among chikungunya isolates based on partial E1 nucleotide sequences. Isolates from the Indian Ocean outbreak (Reunion, Seychelles, Mayotte, Mauritius, Madagascar) represent a distinct clade within a large East, Central and South African (ECSA) phylogroup. Bootstrap resampling values are indicated at major nodes. The branch leading to West-African phylogroup (of length approx. 15%) was shortened for convenience.

[0019]FIG. 3: Proposed evolutionary scenario of chikungunya virus isolates from 1 the Indian Ocean outbreak. The scenario is based on six genome sequences determined by direct sequencing of RT-PCR products obtained using RNA extracts as templates; the sequences thus correspond to consensus sequences (Cons. Seq.) of the possible mixture of coexisting genomes (quasispecies). Inset: number of cases of E1-226A and E1-226V at different time intervals in Reunion Island, based on partial E1 sequences. E1-226V was observed in consensus sequences 2, 3 and 4, and therefore most E1-226V isolates genotyped based on partial E1 sequences are likely related to these genotypes. However, the independent appearance of E1-226V in other genotypes cannot be excluded. Int.: intermediate sequence. The location, size and relative position of the Islands and the African border are indicative. Consensus sequence 1 was obtained from a Reunion patient who traveled back from Comoros in March 2005, and from a Reunion Island patient. Sequences 2 to 4 were sampled in Reunion Island; sequence 5 was sampled in the Seychelles.

[0020]FIG. 4 shows the nucleotide sequence of the genome of a CHIK virus strain according to a preferred embodiment of the invention and more specifically for the preferred strain named 05.115 (SEQ ID NO:1).

[0021]FIG. 5 shows the nucleotide sequence of the genome of a CHIK virus strain according to a preferred embodiment of the invention and more specifically for the preferred strain named 05.209 (SEQ ID NO:2).

[0022]FIG. 6 shows the nucleotide sequence of the genome of a CHIK virus strain according to a preferred embodiment of the invention and more specifically for the preferred strain named 06.21 (SEQ ID NO:3).

[0023]FIG. 7 shows the nucleotide sequence of the genome of a CHIK virus strain according to a preferred embodiment of the invention and more specifically for the preferred strain named 06.27 (SEQ ID NO:4).

[0024]FIG. 8 shows the nucleotide sequence of the genome of a CHIK virus strain according to a preferred embodiment of the invention and more specifically for the preferred strain named 06.49 (SEQ ID NO:5).

[0025]FIG. 9 shows the nucleotide sequence of the genome of a CHIK virus strain according to a preferred embodiment of the invention and more specifically for the preferred strain named 05.61 (SEQ ID NO:6).

[0026]FIG. 10 shows a nucleotide sequence of a fragment of a CHIK virus according to a preferred embodiment of the invention, and more specifically a fragment which codes for the ectodomain of the glycoprotein E2 of the preferred strain named 06.21 (SEQ ID NO:7).

[0027]FIG. 11 shows a nucleotide sequence of a fragment of a CHIK virus according to a preferred embodiment of the invention, and more specifically a fragment which codes for the ectodomain of the glycoprotein E2 of the preferred strain named 06.27 (SEQ ID NO:8).

[0028]FIG. 12 shows a nucleotide sequence of a fragment of a CHIK virus according to a preferred embodiment of the invention, and more specifically a fragment which codes for the ectodomain of the glycoprotein E2 of the preferred strain named 06.49 (SEQ ID NO:9).

[0029]FIG. 13 shows a nucleotide sequence of a fragment of a CHIK virus according to a preferred embodiment of the invention, and more specifically a fragment which codes for the ectodomain of the glycoprotein E2 of the preferred strain named 06.115 (SEQ ID NO:10).

[0030]FIG. 14 shows a nucleotide sequence of a fragment of a CHIK virus according to a preferred embodiment of the invention, and more specifically a fragment which codes for a soluble form of the glycoprotein E2 of the preferred strain named 06.21 (SEQ ID NO:11).

[0031]FIG. 15 shows a nucleotide sequence of a fragment of a CHIK virus according to a preferred embodiment of the invention, and more specifically a fragment which codes for a soluble form of the glycoprotein E2 of the preferred strain named 06.27 (SEQ ID NO:12).

[0032]FIG. 16 shows a nucleotide sequence of a fragment of a CHIK virus according to a preferred embodiment of the invention, and more specifically a fragment which codes for a soluble form of the glycoprotein E2 of the preferred strain named 06.49 (SEQ ID NO:13).

[0033]FIG. 17 shows a nucleotide sequence of a fragment of a CHIK virus according to a preferred embodiment of the invention, and more specifically a fragment which codes for a soluble form of the glycoprotein E2 of the preferred strain named 06.115 (SEQ ID NO:14).

[0034]FIG. 18 shows an amino acid sequence of a preferred CHIK virus polypeptide according to a preferred embodiment of the invention, and related more specifically to the ectodomain of the glycoprotein E2 of the preferred strain named 06.21 (SEQ ID NO:15).

[0035]FIG. 19 shows an amino acid sequence of a preferred CHIK virus polypeptide according to a preferred embodiment of the invention, and related more specifically to the ectodomain of the glycoprotein E2 of the preferred strain named 06.27 (SEQ ID NO:16).

[0036]FIG. 20 shows an amino acid sequence of a preferred CHIK virus polypeptide according to a preferred embodiment of the invention, and related more specifically to the ectodomain of the glycoprotein E2 of the preferred strain named 06.49 (SEQ ID NO:17).

[0037]FIG. 21 shows an amino acid sequence of a preferred CHIK virus polypeptide according to a preferred embodiment of the invention, and related more specifically to the ectodomain of the glycoprotein E2 of the preferred strain named 06.115 (SEQ ID NO:18).

[0038]FIG. 22 shows an amino acid sequence of a preferred CHIK virus polypeptide according to a preferred embodiment of the invention, and related more specifically to a soluble form of the glycoprotein E2 of the preferred strain named 06.21 (SEQ ID NO:19).

[0039]FIG. 23 shows an amino acid sequence of a preferred CHIK virus polypeptide according to a preferred embodiment of the invention, and related more specifically to a soluble form of the glycoprotein E2 of the preferred strain named 06.27 (SEQ ID NO:20).

[0040]FIG. 24 shows an amino acid sequence of a preferred CHIK virus polypeptide according to a preferred embodiment of the invention, and related more specifically to a soluble form of the glycoprotein E2 of the preferred strain named 06.49 (SEQ ID NO:21).

[0041]FIG. 25 shows an amino acid sequence of a preferred CHIK virus polypeptide according to a preferred embodiment of the invention, and related more specifically to a soluble form of the glycoprotein E2 of the preferred strain named 06.115 (SEQ ID NO:22).

[0042]FIG. 26: Repeat Sequence Elements Found in the 3'NTR Region

[0043]A. Alignment of Repeat Sequence Elements found in the 3'NTR region of chikungunya virus genome. All sequences form conserved and stable stem-loop structures in which the less conserved nucleotides around position 20 constitute the loop. Three RSE are found in all chikungunya genomes. The first one (RSE1) is inserted before the internal poly-A sequence of S27 genome [9], whereas the two others are found downstream this motif.

[0044]B. Predicted secondary structure for RSE1 of isolate 05-115.

[0045]FIG. 27: Focus Phenotype of Chikungunya Viruses on AP61 Cells by Focus Immunoassay

[0046]Mosquito AP61 cells in 24-well plates were infected with CHIK virus stocks grown on mosquito cells (virus titers 2-5×10 8 FFU. mL-1) at 0.0001 (top well) or 0.00001 (bottom well) multiplicity of infection. Infected cells were overlaid with CMC in Leibovitz L15 growth medium with 2% FBS for 2 days to allow focus development at 28° C. The cells were fixed with 3% PFA in PBS, permeabilized with Triton X-100 in PBS, and foci of CHIK virus replication were immunostained with mouse anti-CHIK HMAF (dilution 1:2,000) and peroxidase-conjugated goat anti-mouse Ig (dilution 1:100).

[0047]FIG. 28: Viral preparation containing pE2. pE2 proteins detected by anti-CHIK antibodies.

[0048]FIG. 29: Alignment of nucleotide sequences encoding soluble form of E2 glycoprotein (E2-1 to E2-361) from Indian Ocean CHIK virus strains -21, -27, -49 and -115.

[0049]FIG. 30: Primer sequences (SEQ ID NO:79 and 80) used for the amplification and cloning of the soluble form of the E2 (E2-1 to E2-364) (N-terminal and C-terminal nucleic acid fragment: SEQ ID NO:81 and 82; N-terminal and C-terminal protein fragment: SEQ ID NO:83 and 84) from CHIK virus into the shuttle vector pMT2/BiP/V5-HisA.

[0050]FIG. 31: SDS-PAGE showing CHIK-sE2 staining by Coomassie blue.

[0051]FIG. 32: Immunoblot analysis of highly purified CHIK sE2 protein.

[0052]FIG. 33: Construct of the TRIP vector expressing the secreted soluble form of the E2 glycoprotein (sE2) from Chikungunya virus La Reunion 05 strains.

[0053]FIG. 34 shows the nucleotide sequence coding the secreted soluble form of the E2 glycoprotein (sE2) into the TRIP vector (SEQ ID NO:85).

[0054]FIG. 35: Immunofluorescent (IF) assay using anti-CHIK antibodies on TRIP/CHIK.sE2-transduced 293 cells.

[0055]FIG. 36 shows a direct ELISA with 10^-4 mL of enriched pE2 protein per well. Antigens were tested respectively with a mouse anti-DEN1 (dilution 1:1000), anti-WN (dilution 1:1000) and anti-CHIK (dilution 1:10 000).

[0056]FIG. 37 shows an amino acid sequence of the ORF 2 (structural proteins) of the CHIK S27 strain (GenBank AF339485; SEQ ID NO: 23).

[0057]FIG. 38 shows an amino acid sequence of the ORF 2 (structural proteins) of a preferred CHIK virus according to a preferred embodiment of the invention, namely the 05.61 strain (SEQ ID NO: 24).

[0058]FIG. 39 shows an amino acid sequence of the ORF 2 (structural proteins) of a preferred CHIK virus according to a preferred embodiment of the invention, namely the 05.209 strain (SEQ ID NO: 25).

[0059]FIG. 40 shows an amino acid sequence of the ORF 2 (structural proteins) of a preferred CHIK virus according to a preferred embodiment of the invention, namely the 05.115 strain (SEQ ID NO: 26).

[0060]FIG. 41 shows an amino acid sequence of the ORF 2 (structural proteins) of a preferred CHIK virus according to a preferred embodiment of the invention, namely the 06.49 strain (SEQ ID NO: 27).

[0061]FIG. 42 shows an amino acid sequence of the ORF 2 (structural proteins) of a preferred CHIK virus according to a preferred embodiment of the invention, namely the 06.27 strain (SEQ ID NO: 28).

[0062]FIG. 43 shows an amino acid sequence of the ORF 2 (structural proteins) of a preferred CHIK virus according to a preferred embodiment of the invention, namely the 06.21 strain (SEQ ID NO: 29).

[0063]FIG. 44 shows an amino acid sequence of the ORF 1 (non-structural proteins) of a preferred CHIK virus according to a preferred embodiment of the invention, namely the 05.61 strain (SEQ ID NO: 30).

[0064]FIG. 45 shows an amino acid sequence of the ORF 1 (non-structural proteins) of a preferred CHIK virus according to a preferred embodiment of the invention, namely the 05.209 strain (SEQ ID NO: 31).

[0065]FIG. 46 shows an amino acid sequence of the ORF 1 (non-structural proteins) of a preferred CHIK virus according to a preferred embodiment of the invention, namely the 05.115 strain (SEQ ID NO: 32).

[0066]FIG. 47 shows an amino acid sequence of the ORF 1 (non-structural proteins) of a preferred CHIK virus according to a preferred embodiment of the invention, namely the 06.49 strain (SEQ ID NO: 33).

[0067]FIG. 48 shows an amino acid sequence of the ORF 1 (non-structural proteins) of a preferred CHIK virus according to a preferred embodiment of the invention, namely the 06.27 strain (SEQ ID NO: 34).

[0068]FIG. 49 shows an amino acid sequence of the ORF 1 (non-structural proteins) of a preferred CHIK virus according to a preferred embodiment of the invention, namely the 06.21 strain (SEQ ID NO: 78).

[0069]FIG. 50: Evaluation of anti-CHIK E2 Mab reactivity by ELISA.

[0070]FIG. 51: Evaluation of anti-CHIK E2 MAb reactivity on CHIK virions by ELISA.

[0071]FIG. 52: Immunofluorescence (IF) analysis of anti-CHIK E2 Mab reactivity on

[0072]CHIKV-infected Vero cells.

[0073]FIG. 53: Immunofluorescence (IF) analysis of anti-CHIK E2 Mab reactivity on TRIP/CHIK.sE2-transduced 293A cells.

[0074]FIG. 54: Anti-CHIK E2 Mab binding on cell surface of CHIK virus-infected Vero cells by FACS analysis.

[0075]FIG. 55: Western blot analysis of CHIKsE2 expression in TRIP/CHIK.sE2-transduced 293A cells.

DETAILED DESCRIPTION OF THE INVENTION

[0076]In the present study, the inventors determined the nearly complete nucleotide sequences of viruses isolated from six patients originating from Reunion and Seychelles Islands. The present invention allows to determine the genome structure as well as the unique molecular features of the Indian Ocean outbreak isolates, which distinguish them from other reported CHIKV and alphavirus sequences.

[0077]As one in the art may appreciate, the originality of the present invention is the identification of novel strains of the Chikungunya (CHIK) virus which are distinguished from CHIK virus of the prior art, and the use of these CHIK strains and the polypeptides and the polynucleotides encoding same derived from their genome in the diagnostic, prevention and/or treatment of arbovirosis.

[0078]According to a first aspect, the present invention concerns an isolated and purified wild strain of chikungunya virus (CHIKV) capable of in vitro infecting human cells. Preferably, the present invention concerns a wild strain of CHIK virus which exhibits the same characteristics than those selected from the group consisting of the isolates 05.115, 05.61, 05.209, 06.21, 06.27 and 06.49. According to a preferred embodiment, the strains that are within the scope of the present invention are characterized in that their genome comprises at least one mutation when compared to the sequence of the genome of the CHIK virus strain S-27 (GenBank AF339485). Also within the scope of the invention, is any strain grown or obtained by cell culture from a sample of a preferred CHIK strain of the invention. The genome of the preferred strains according to the present invention comprises a sequence as shown in FIG. 4, 5, 6, 7, 8 or 9 (SEQ ID NO: 1, 2, 3, 4, 5 or 6).

[0079]According to another aspect, the present invention provides an isolated and purified strain of chikungunya virus (CHIKV) comprising at least one mutation in structural protein E1 and/or in structural protein E2, and more particularly in their ectodomain region. According to a preferred embodiment, the strain of the invention is characterized by the fact that its genome comprises at least one mutation in the E2 protein at a position homologous to amino acid position 382, 399, 404, 485, 489, 506, 536, 624, 637, 669, 700 or 711 of SEQ ID NO: 23 (FIG. 37). More particularly, the mutation is preferably selected from the group consisting of G382K, I399M, G404E, N485T, A489T, L506M, 1536T, S629N, T637M, A669T, S700T and V711A as shown in Table 6. According to another preferred embodiment, the strain of the invention is characterized by the fact that its genome comprises at least one mutation in the E1 protein at a position homologous to amino acid position 1035, 1078, 1093 or 1131 of SEQ ID NO: 23. More particularly, the mutation is preferably selected from the group consisting of A1035V, M1078V, D1093E and V1131A as shown in Table 6. Most preferably, the mutation in the E1 protein is A1035V.

[0080]As use herein, the expression "at a position homologous to an amino acid position" of a protein, refers to amino acid positions that are determined to correspond to one another based on sequence and/or structural alignments with a specified reference protein. For instance, in a position corresponding to an amino acid position of a CHIK virus structural protein set forth as SEQ ID NO: 1 can be determined empirically by aligning the sequences of amino acids set forth in SEQ ID NO: 1 with a particular CHIK virus structural protein. Homologous or corresponding positions can be determined by such alignment by one of skill in the art using manual alignments or by using the numerous alignment programs available (for example, BLASTP). Homologous or corresponding positions also can be based on structural alignment, for example by using computers simulated alignments of protein structure. Recitation that amino acids of a polypeptide correspond to amino acids in a disclosed sequence refers to amino acids identified upon alignment of the polypeptide with the disclosed sequence to maximize identity or homology (where conserved amino acids are aligned) using a standard algorithm, such as the GAP algorithm. As used herein, "at a position homologous to" refers to a position of interest (i.e., base number or residue number) in a nucleic acid molecule or protein relative to the position in another reference nucleic acid molecule or protein. The position of interest to the position in another reference protein can be in, for example, an amino acid sequence from the same protein of another CHIK strain. Homologous positions can be determined by comparing and aligning sequences to maximize the number of matching nucleotides or residues, for instance, such that identity between the sequences is greater than 95%, preferably greater than 96%, more preferably greater than 97%, even more preferably greater than 98% and most preferably greater than 99%. The position of interest is then given the number assigned in the reference nucleic acid molecule.

[0081]Another aspect of the invention concerns an isolated and purified polynucleotide comprising all or part of the sequence as shown in FIG. 4, 5, 6, 7, 8 or 9 (SEQ ID NO: 1, 2, 3, 4, 5 or 6).

[0082]Another aspect of the invention concerns a fragment of the polynucleotide of the invention characterized by the fact that it codes for the glycoprotein E1 or E2, and more preferably for their ectodomain region. Advantageously, the fragment of the invention when coding for the E2 ectodomain, comprises, or more preferably, consists of a nucleotide sequence as shown in FIG. 10, 11, 12 or 13 (SEQ ID NO: 7, 8, 9 or 10).

[0083]Yet another aspect of the invention concerns a fragment of the polynucleotide of the invention characterized by the fact that it codes for a soluble form of glycoprotein E2. According to a preferred embodiment, the soluble fragment of glycoprotein E2 comprises or more preferably consists of a nucleotide sequence as shown in FIG. 14, 15, 16 or 17 (SEQ ID NO. 11, 12, 13 or 14).

[0084]As one skilled in the art may appreciate, a fragment as contemplated by the present invention may be obtained by: [0085]use of restriction enzymes wherein their cleavage sites are present in the polynucleotide comprising said fragment; [0086]amplification with specific primers for said fragment; [0087]in vitro transcription; or [0088]chemical synthesis.

[0089]According to another aspect, the present invention is concerned with an isolated and purified polypeptide encoded by a polynucleotide or by a fragment of the invention. As used herein, the terms "polypeptide" and "protein" are used interchangeably to denote an amino acid polymer or a set of two or more interacting or bound amino acid polymers.

[0090]By "isolated" is meant, when referring to a polypeptide, that the indicated molecule is separate and discrete from the whole organism with which the molecule is found in nature or is present in the substantial absence of other biological macro-molecules of the same type. The term "isolated" with respect to a polynucleotide is a nucleic acid molecule devoid, in whole or part, of sequences normally associated with it in nature; or a sequence, as it exists in nature, but having heterologous sequences in association therewith; or a molecule disassociated from the chromosome.

[0091]Broadly defined, the terms "purified polypeptide" or "purified polynucleotide" refer to polypeptides or polynucleotides that are sufficiently free of other proteins or polynucleotides, or carbohydrates, and lipids with which they are naturally associated. The polypeptide or polynucleotide may be purified by any process by which the protein or polynucleotide is separated from other elements or compounds on the basis for instance, of charge, molecular size, or binding affinity.

[0092]The preferred peptides of the invention comprise at least one amino acid substitution compared with the amino acid sequence of strain S-27 (GenBank AF339485) and are derived from the sequence of a protein coded by a fragment of the invention. Preferably, a purified polypeptide of the invention comprises all or part of the amino acid sequence of a CHIK virus ORF 1 or 2 contemplated by the present invention such as one defined in any one of SEQ ID NOS 24 to 29 (ORF 2) or of SEQ ID NOS 30 to 34 and 78 (ORF 1). More preferably, a purified polypeptide of the invention comprises all or part of the amino acid sequence of a glycoprotein E2 contemplated by the present invention such as one defined in any one of SEQ ID NOS 15 to 18 (FIGS. 18 to 21). Even more preferably, a purified polypeptide of the invention comprises all or part of the amino acid sequence of a soluble form of glycoprotein E2 contemplated by the present invention such as one defined in any one of SEQ ID NOS 19 to 22 (FIGS. 22 to 25).

[0093]The present invention is also concerned with a vector comprising a polynucleotide of the invention or a fragment of a polynucleotide of the invention. As used herein, the term "vector" refers to a polynucleotide construct designed for transduction/transfection of one or more cell types. Vectors may be, for example, "cloning vectors" which are designed for isolation, propagation and replication of inserted nucleotides, "expression vectors" which are designed for expression of a nucleotide sequence in a host cell, or a "viral vector" which is designed to result in the production of a recombinant virus or virus-like particle, or "shuttle vectors", which comprise the attributes of more than one type of vector. Preferred vector are those deposited at the CNCM (Collection Nationale de Cultures de Microorganismes), 28 rue du Docteur Roux, 75724 PARIS Cedex 15, France, on Mar. 15, 2006 under accession numbers I-3587, I-3588, I-3589 and I-3590.

[0094]Another preferred vector contemplated by the present invention is the plasmid called TRIP-CHIK.sE2 which has been deposited at the CNCM (Collection Nationale de Cultures de Microorganismes), 28 rue du Docteur Roux, 75724 PARIS Cedex 15, France, on Mar. 14, 2007, under accession number I-3733. Such a vector comprises a fragment which codes for a soluble form of the glycoprotein E2 of the invention. This preferred vector has been optimised for efficient production of the recombinant E2 protein into mammalian cells. As used herein, the term "optimised" means that the vector incorporates regulation sequences, such as a signal peptide sequence, in order to provide adequate expression of the desired encoded protein.

[0095]In a related aspect, the present invention provides a host cell comprising a vector as defined above. The term "host cell" refers to a cell that has a new combination of nucleic acid segments that are not covalently linked to each other in nature. A new combination of nucleic acid segments can be introduced into an organism using a wide array of nucleic acid manipulation techniques available to those skilled in the art. A host cell can be a single eukaryotic cell, or a single prokaryotic cell, or a mammalian cell. The host cell can harbor a vector that is extragenomic. An extragenomic nucleic acid vector does not insert into the cell's genome. A host cell can further harbor a vector or a portion thereof that is intragenomic. The term intragenomic defines a nucleic acid construct incorporated within the host cell's genome. A preferred host cell of the invention E. coli such as the one containing a vector of the invention and deposited at the CNCM (Collection Nationale de Cultures de Microorganismes), 28 rue du Docteur Roux, 75724 PARIS Cedex 15, France, on Mar. 15, 2006 under accession numbers I-3587, I-3588, I-3589 and I-3590 and on Mar. 14, 2007 under accession number I-3733.

[0096]The present invention is further concerned with a monoclonal antibody or polyclonal antibodies, or fragments thereof, that specifically bind to a polypeptide of the invention. As used herein, the term "specifically binds to" refers to antibodies that bind with a relatively high affinity to one or more epitopes of a protein of the invention, but which do not substantially recognize and bind to molecules other than the one(s) of interest. As used herein, the term "relatively high affinity" means a binding affinity between the antibody and the protein of interest of at least 10^-6 M, and preferably of at least about 10^-7 M and even more preferably 10^-8 M to 10^-10 M. Determination of such affinity is preferably conducted under standard competitive binding immunoassay conditions which is common knowledge to one skilled in the art.

[0097]As used herein, the term "antibody" refers to a glycoprotein produced by lymphoid cells in response to a stimulation with an immunogen. Antibodies possess the ability to react in vitro and in vivo specifically and selectively with an antigenic determinant or epitope eliciting their production or with an antigenic determinant closely related to the homologous antigen. The term "antibody" is meant to encompass constructions using the binding (variable) region of such an antibody, and other antibody modifications. Thus, an antibody useful in the method of the invention may comprise a whole antibody, an antibody fragment, a polyfunctional antibody aggregate, or in general a substance comprising one or more specific binding sites from an antibody. The antibody fragment may be a fragment such as an Fv, Fab or F(ab')₂ fragment or a derivative thereof, such as a single chain Fv fragment. The antibody or antibody fragment may be non-recombinant, recombinant or humanized. The antibody may be of an immunoglobulin isotype, e.g., IgG, IgM, and so forth. In addition, an aggregate, polymer, derivative and conjugate of an immunoglobulin or a fragment thereof can be used where appropriate.

[0098]Another aspect of the invention is the use of an element selected from the group consisting of a strain, a polynucleotide, a fragment, a vector, a host cell, a polypeptide and an antibody of the invention for either the detection of a CHIKV associated to an arbovirosis, or for the preparation of a composition that prevents and/or treats an arbovirosis.

[0099]Another aspect of the present invention relates to a composition for treating and/or preventing an arbovirosis. The composition of the present invention advantageously comprises at least one element selected from the group consisting of a strain, a polynucleotide, a fragment, a vector, a host cell, a polypeptide and an antibody of the invention. The composition of the invention may further comprise an acceptable carrier. In a related aspect, the invention provides a method for treating and/or preventing an arbovirosis. The method comprises the step of administering to a subject in need thereof a composition of the invention.

[0100]As used herein, the term "treating" refers to a process by which the development of an infection from a CHIKV is affected or completely eliminated. As used herein, the term "preventing" refers to a process by which the CHIKV infection is obstructed or delayed.

[0101]As used herein, the expression "an acceptable carrier" means a vehicle for containing the components (or elements) of the composition of the invention that can be administered to a animal host without adverse effects. Suitable carriers known in the art include, but are not limited to, gold particles, sterile water, saline, glucose, dextrose, or buffered solutions. Carriers may include auxiliary agents including, but not limited to, diluents, stabilizers (i. e., sugars and amino acids), preservatives, wetting agents, emulsifying agents, pH buffering agents, viscosity enhancing additives, colors and the like.

[0102]The amount of components of the composition of the invention is preferably a therapeutically effective amount. A therapeutically effective amount of components of the composition of the invention is the amount necessary to allow the same to perform their preventing and/or treating role against a CHIKV infection without causing overly negative effects in the host to which the composition is administered. The exact amount of components to be used and the composition to be administered will vary according to factors such as the mode of administration, as well as the other ingredients in the composition.

[0103]The composition of the invention may be given to a host (such as a human) through various routes of administration. For instance, the composition may be administered in the form of sterile injectable preparations, such as sterile injectable aqueous or oleaginous suspensions. These suspensions may be formulated according to techniques known in the art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparations may also be sterile injectable solutions or suspensions in non-toxic parenterally-acceptable diluents or solvents. They may be given parenterally, for example intravenously, intramuscularly or sub-cutaneously by injection, by infusion or per os. Suitable dosages will vary, depending upon factors such as the amount of each of the components in the composition, the desired effect (short or long term), the route of administration, the age and the weight of the host to be treated. Any other methods well known in the art may be used for administering the composition of the invention.

[0104]Yet another aspect of the invention is the use of a composition as defined hereabove for the preparation of a medicament for treating and/or preventing an arbovirosis in a subject in need thereof.

[0105]Yet another aspect of the invention is to provide a kit for the detection of a CHIKV associated to an arbovirosis, comprising at least one element selected from the group consisting of a strain, a polynucleotide, a fragment, a vector, a host cell, a polypeptide and an antibody of the invention. Kits according to this embodiment of the invention may comprise packages, each containing one or more of the above mentioned elements (typically in concentrated form) which are required to perform the respective diagnostic tests.

EXAMPLES

[0106]The examples here below will highlight other characteristics and advantages of the present invention, and will serve to illustrate the scope of the use of the present invention and not to limit its scope. Modifications and variations may be made without departing from the spirit and the scope of the invention. Although it is possible to use other methods or products equivalent to those that are found here below to test or to realize the present invention, the preferred material and methods are described.

Example 1

Identification and Characterization of CHIK Viruses Causing the Indian Ocean Outbreak

[0107]The inventors (as sometimes referred therein as "we") report the nearly complete genome sequence of six selected clinical isolates, along with partial sequences of glycoprotein E1 from a total of 60 patients from Reunion, Seychelles, Mauritius, Madagascar and Mayotte Islands. The present results indicate that the outbreak was initiated by a strain related to East-African isolates, from which viral variants have evolved following a traceable microevolution history. Unique molecular features of the outbreak isolates were identified. Notably, in the region coding for the non-structural proteins, ten amino acid changes were found, three of which being located in alphavirus conserved positions of nsP2 (which contains helicase, protease and RNA triphosphatase activities) and of the polymerase nsP4. The sole isolate obtained from the cerebrospinal fluid of a patient showed unique changes in nsP1 (T301I), nsP2 (Y642N) and nsP3 (E460 deletion). In the structural protein region, two noteworthy changes (A226V and D284E) were observed in the membrane fusion glycoprotein E1. Homology 3D modelling allowed mapping of these two changes to regions that are important for virion assembly and for membrane fusion. Change E1-A226V was absent in the initial strains but was observed in >85% of subsequent viral sequences from Reunion, denoting evolutionary success possibly due to adaptation to the mosquito vector.

Material and Methods

[0108]Patients. The 60 patients for whom partial or complete CHIKV nucleotide sequences were determined originated from Reunion (N=43), Seychelles (N=3), Madagascar (N=7), Mayotte (N=4) and Mauritius (N=3). Characteristics of the patients and biological samples are listed in Table 1.

[0109]Virus isolation and RNA extraction. Viruses were isolated either from serum or cerebrospinal fluid (CSF) (Table 1). Briefly, C6-36 Aedes albopictus cells were inoculated with 1 ml of serum or CSF diluted 1:10 in L15 medium (Gibco). The cells were grown at 28° C. in L15 supplemented with 5% foetal bovine serum and 10% tryptose-phosphate. Cells and supernatants were harvested after the first passage (5 days) and the second passage (7 days). The virus isolates were identified as CHIKV by indirect immunofluorescence, using CHIKV hyper immune ascitic fluid. In the case of isolates 05.115, 06.21, 06.27 and 06.49 whose genomes were sequenced, absence of yellow fever, dengue and West Nile viruses was confirmed by indirect immunofluorescence using specific sera. RNA was extracted using the QIAAmp Viral Minikit (Qiagen, France).

[0110]Nucleotide sequencing. Primers (Table 4) were designed based on the nucleotide sequence 20 of the S27 strain. RT-PCR was performed using the Titan One Tube RT-PCR kit (Roche, France). RT-PCR fragments were purified by ultrafiltration prior to sequencing (Millipore, France). Sequencing reactions were performed using the BigDye Terminator v1.1 cycle sequencing kit (Applied Biosystems, USA) and purified by ethanol precipitation. Sequence chromatograms were obtained on automated sequence analysers ABI3100 or ABI3700 (Applied Biosystems). All amplicons were sequenced on both strands.

[0111]Assembly of genome sequences and sequence analysis. Contig assembly was performed independently by distinct operators and software, using either BioNumerics version 4.5 (Applied-Maths, Sint-Martens-Latem, Belgium) or PhredPhrap/Consed [11]. Both analyses yielded exactly the same consensus sequence for all strains. A single contig of 11,601 nt was obtained for five isolates, whereas for strain 05.61, a sequence portion was missing, between S27 positions 5,246 to 5,649 (positions 390 to 524 of nsP3). Sequence alignments and computation of substitution tables were performed using programs BioNumerics, DNASP version 4.10 [12] and DAMBE version 4.2.13 [13]. Alignments of nucleotide and amino acid sequences against selected alphavirus sequences were performed with the ClustalW1.7 software [14]. Sequence identities were computed with the Phylip package [15]. RNA secondary structure was predicted with the Vienna RNA secondary structure server [16]. Neighbor-joining trees were constructed using MEGA version 3.1 [17] with the Kimura-2 parameter corrections of multiple substitutions. Reliability of nodes was assessed by bootstrap resampling with 1,000 replicates. Amounts of synonymous substitutions per synonymous site (Ks) and of non synonymous substitutions per non synonymous site (Ka) were estimated using DNASP. RDP2 [18] was used to detect putative mosaic sequences.

[0112]3D structure modeling. The crystallographic structure of the ectodomain of the glycoprotein E1 of Semliki Forest Virus (SFV) at neutral pH [19]; Protein Data Bank code 2ALA) was used as a template to model and analyze the two amino acid mutations of the Indian Ocean isolates. FIG. 2 was prepared using the program RIBBONS [20].

[0113]Detection of viral foci by immunological staining. Aedes pseudoscutellaris AP61 cells were grown in a 24-well tissue culture plates in Leibovitz L-15 growth medium with 10% heat inactivated fetal calf serum (FCS) for 24 h. Mosquito cell monolayers were washed once with Leibovitz L-15 and 0.2 ml Leibovitz L-15/2% FCS were added. Cells were infected with CHIK virus in 0.2 ml of Leibovitz L-15/2% FCS and incubated at 28° C. for 1 h. Overlay medium consisting of 0.4 ml of Leibovitz L-15/2% FBS and carboxymethylcellulose (CMC) (1.6%) was then added and the tissue culture plates were incubated at 28° C. for 2 days. Foci of infected cells were visualized by focus immunoassay (FIA). The cells were washed with PBS, fixed with 3% paraformaldehyde (PFA) in PBS for 20 min, and permeabilized with 0.5% Triton X-100 in PBS for 4 min at room temperature. The fixed cells were incubated for 20 min at 37° C. with 1:2,000 dilution of hyperimmune mouse ascitic fluid (HMAF) directed against CHIKV. Goat anti-mouse IgG, horseradish peroxidase conjugated was used as the second antibody (1:100 dilution) at 37° C. for 20 min. Foci were visualized with DAB Peroxidase Substrate (Sigma).

[0114]1. Genome Structure and Molecular Signatures of the Indian Ocean Outbreak Chikungunya Viruses

[0115]Genome organization. We determined the nearly complete genome sequences of six CHIKV isolates (05.115, 05.61, 05.209, 06.21, 06.27 and 06.49) representing distinct geographic origins, time points and clinical forms (Table 1) of the Indian Ocean outbreak of chikungunya virus. 11,601 nucleotides were determined, corresponding to positions 52 (5'NTR) to 11,667 (3'NTR, end of third Repeat Sequence Element) in the nucleotide sequence of the 1952 Tanzanian isolate S27 (total length 11,826 nt). There were three insertion/deletion events between S27 and Reunion isolates, two of which were observed in the 3'NTR. First, the internal poly-A stretch of 14 nucleotides observed in S27 (11,440-11,443) and corresponding to a probable internal poly-A site [9] was replaced by a stretch of only 5 A in Indian Ocean isolates, similar to what was observed in other chikungunya viruses, e.g. the Ross strain (accession no.: AF490259). Second, one A was missing in Indian Ocean isolates in a 5-A stretch at S27 position 11,625. Finally, one codon was missing in isolate 06.27, corresponding to nsP3 codon 460, at which all other Indian Ocean isolates analyzed and available alphavirus sequences are GAA, coding for Glu.

[0116]The genome sequences of the six isolates presented therein was similar to those previously reported for alphaviruses [9, 21, 22]. Coding sequences consisted of two large open reading frames (ORF) of 7,422 nt and 3,744 nt encoding the non-structural polyprotein (2,474 amino-acids) and the structural polyprotein (1,248 amino-acids), respectively. The non structural polyprotein is the precursor of proteins nsP1 (535 aa), nsP2 (798 aa), nsP3 (530 aa) and nsP4 (611 aa), and the structural polyprotein is the precursor of proteins C (261 aa), p62 (487 aa, precursor to E3-64 aa--and E2-423 aa), 6K (61 aa), and E1 (439 aa). Cleavage sites characteristic of the alphavirus family in the non-structural and structural polyproteins were conserved. Glycosylation sites in E3, E2 and E1 were also conserved. A 65 nt junction sequence was identified between the stop codon (TAG, 7499-7501) of the non-structural ORF and the start codon (7567-7569) of the structural ORF. The 5' non-translated region (5'NTR) ended at position 76. The 3'NTR region started at position 11,314 and contained three repeat sequence elements (RSE) with predicted secondary structures (FIG. 26) that were consistent with previous work [9].

[0117]Differences between Indian Ocean outbreak isolates and strain S27. Compared to strain S27, Reunion isolate 05.115 showed 28 aa changes (1.13%) in the non-structural proteins (Table 5, with the highest proportion in nsP3 (2.26%) and the lowest in nsP2 (0.6%). Ten out of 12 amino acid changes in nsP3 were concentrated between positions 326 and 524 (5.0% variation), similar to findings in ONN viruses [23]. One important difference with S27 was that the Indian Ocean isolates exhibited an opal stop codon (UGA) at nsP3 codon 524, instead of Arg (CGA) in S27. This opal codon was observed in related alphaviruses [9, 22, 23], and is believed to regulate the expression of nsP4, the putative RNA polymerase, by a read-through mechanism [21, 24].

[0118]Compared to S27, the structural proteins showed 21 (1.68%, for 05.115) to 22 (1.76%, for other isolates) amino-acid substitutions in Indian Ocean isolates (Table 6). Notably, envelope protein E2 showed the highest variation, with 14 (3.3%) aa changes, higher than envelope protein E1 (0.68%) and the capsid protein (0.38%). The ratio of rates of evolution of synonymous and non-synonymous sites (Ks/Ka) between S27 and 05.115 isolates was 11.0 for the whole polyprotein, whereas it was only 6.12 for protein E2, probably indicative of a positive selection in favor of amino-acid changes in this immunogenic protein. By comparison, Ks/Ka was 18.75 for the non-structural polyprotein.

[0119]Indian Ocean outbreak molecular signatures in non-structural proteins and phenotypic variation. Ten positions (excluding polymorphic positions) had aa that were unique to the non-structural proteins of outbreak isolates, when compared to other CHIKV sequences (Table 2). First, nsP2-54 was Asn in Indian Ocean isolates and in SFV, but was Ser in all other sequences. Second, nsP2-374 was Tyr in Indian Ocean isolates, but was His or Asn in other alphavirus sequences (Table 2). Third, position 500 in nsP4 was Leu in the Indian Ocean sequences instead of Gln in the four other reported CHIKV sequences. Interestingly, this position, which is about 30 aa from the catalytic "GDD" motif, is a strictly conserved Glu in all other alphaviruses. The remaining seven changes took place in relatively variable regions.

[0120]Additional specific changes were observed in isolates 05.209 (S358P) and 06.27 (nsP1-T3011, nsP2-Y642N, and nsP3-460del). Notably, our phenotypic assays conducted in parallel showed differences for strain 06.27. Focus immunoassay showed that CHIKV stocks 05.115, 06.21, 06.27 and 06.49 formed mixtures of foci with different sizes on Ae. Albopictus C6/36 (data not shown) and Ae. pseudoscuterallis AP61 cells (FIG. 27). Interestingly, only isolate 06-27 formed medium foci, whereas others formed minutes and small foci. The particular phenotype of 06-27 could be linked to the observed aa differences in the non structural proteins, which are involved in the viral replication [21].

[0121]Indian Ocean molecular signatures in structural proteins and 3D modelling. When analyzing the aa sequences of the structural proteins, seven positions (four in E2, one in 6K and two in E1) were found to be unique to isolates from the Indian Ocean outbreak (Table 2). Two of these were located in the E2 ectodomain, with Thr 164 and Met 312 being identified in our isolates instead of Ala and Thr, respectively, in all other available CHIKV sequences (Table 2). The first of these two positions is variable in alphaviruses; it lies in a region defined previously as containing neutralizing epitopes [5, 25]. At position 312, Thr is present in other CHIKV, in ONNV and in SFV, but varies in other alphaviruses; it lies in a region identified as important for E1-E2 oligomerization [5, 25].

[0122]In E1,two crucial substitutions were observed, one at residue 284, specific to Indian Ocean isolates, and one at residue 284, present in 3 out of 6 Indian isolates (06.21, 06.27 and 06.49). Both mutations were mapped on the 3D structure (modeled from the crystal structure of SFV E1) in FIG. 1. Interestingly, residue 226 is Ala in all reported CHIKV sequences (Table 2), and was also Ala in the first of our Indian Ocean isolates sequenced here (05.61 and 05.115, obtained at the beginning of the outbreak). All subsequent isolates (obtained from patients collected in November and December 2005) displayed a Val residue at this position. Although position 226 is relatively variable among alphaviruses, it was observed that a single mutation at this position (Pro to Ser) allowed SFV to adapt to growth in cholesterol-depleted insect cells [26, 27].

[0123]The other unique aa observed in E1 from Indian Ocean isolates was Glu 284. This is a highly conserved position in E1, which displays an Asp in the majority of alphaviruses or an Asn in SIN (Table 2). This amino acid is located at the interface between E1 protomers at the surface of the virion, participating in contacts that make up the icosahedral E1 scaffold (FIG. 1).

[0124]2. Phylogenetic Analysis

[0125]Previous work based on E1 protein sequences showed strong phylogeographic structure of the chikungunya virus species [6, 10]. In order to determine the progenitor phylogroup from which the Indian Ocean outbreak isolates emerged, we compared a 1,044 nt region within the E1 coding sequence (positions 271 to 1314, i.e., codons 91 to 438) from 63 biological specimens from 60 patients from Reunion, Seychelles, Madagascar, Mayotte and Comoros (Table 1) with 29 other available chikungunya sequences (Table 7). Phylogenetic analysis (FIG. 2) clearly demonstrated that the current Indian Ocean isolates represent a homogeneous clade within a broad group (group ECSA) comprising isolates from East, Central and South Africa (ECSA, FIG. 2). The isolates from an outbreak in Democratic Republic of the Congo [6] also formed a homogeneous clade within group ECSA. There was no ECSA group member showing a significantly closer relationship with the Indian Ocean isolates. Asian isolates were less related to Indian Ocean isolates and constituted the sister group of group ECSA, whereas West-African isolates were even more divergent. Inclusion of other alphaviruses, including the closest relative ONN, placed the root of the chikungunya isolates on the branch leading to the West-African phylogroup (data not shown).

[0126]Comparison of the sequences of Indian Ocean outbreak isolates to the S27 sequence revealed 316 (2.7%) nucleotide substitutions in isolate 05.115 (Table 8). The Asian clade Nagpur strain showed 5.1% average nucleotide divergence from 05.115, whereas the West-African clade Senegal strain 37997 displayed 15% difference (Table 8). Interestingly, the latter strain showed complete conservation of an 87 nucleotides portion (9,958-10,045, at the junction between structural proteins 6K and E1) with East-African and Indian Ocean outbreak isolates. Sequence identity in this portion may reflect a past event of genetic recombination between West-African and East/Central-African strains. Differently, we did not find statistical support (P>7E-2) for sequence mosaicism or recombination since the split between S27 and Reunion isolates, although some genomic regions differed in their density of nucleotide polymorphisms.

[0127]3. Genotypic and Phenotypic Variation Among Indian Ocean Outbreak Isolates and Microevolutionary Scenario

[0128]Specific aa changes in the non-structural proteins were observed in the isolates 05.209 (S358P) and 06.27 (nsP1-T3011, nsP2-Y642N, and nsP3-460del). In the structural proteins, change E1-A226V was observed in isolates 06.21, 06.27 and 06.49, and change E2-Q146R in the Seychelles isolate 05.209. In addition to these non-synonymous changes, there were 8 silent substitutions, observed in 05.209, 06.27 and 06.49 (Table 3).

[0129]A history of probable sequence evolution that occurred during the outbreak (FIG. 3) was deduced from the 14 amino-acid variations observed among the six complete genomes (Table 3). Isolate 05.61 was initially selected for genome analysis because it was isolated in March 2005, at the onset of the outbreak, from a Reunion patient returning 1 turning from Comoros Island, where the outbreak had been going on since January 2005. Remarkably, the isolates 05.61 and 05.115 (which was the second earliest isolate analyzed), the African isolate S27 and previous unrelated chikungunya isolates from Africa and Asia were identical at all 14 polymorphic sites. Therefore, the consensus sequence of isolates 05.61 and 05.115 (consensus sequence 1) likely represents the ancestral genotype of the Reunion outbreak. Distribution of the 14 polymorphisms suggested that this founder gave rise to three consensus sequences that likely evolved in four steps. First, substitution at genome position 10,670 (causing the E1 A226V change) gave rise to consensus sequence 2, represented by the late-November 2005 isolate 06.21. Second, a G to A synonymous substitution at position 6,547 (nsP4) led to an intermediate sequence, which itself gave rise to two late sequences: consensus sequence 3 (isolate 06.27), following four additional substitutions and one codon deletion (Table 3), and consensus sequence 4 (06.49), which arose after three distinct synonymous substitutions (Table 3). A fifth consensus sequence was represented by the Seychelles isolate 05.209 alone, which exhibited four substitutions (two of them causing aa changes in nsP3-S358P and in E2-Q146R) compared to consensus sequence 1 (FIG. 3).

[0130]Since Reunion isolates had E1-226A at the beginning of the outbreak and E1-266V A at the beginning of the outbreak and E1-266V later in the epidemics, we compared residue 226 in 57 additional sequences (57 sequences from 54 sera and 3 CSF) from the Indian Ocean epidemic. Remarkably, the nature of E1-226 differed totally on Reunion Island before and after the winter season. Five sequences from patients sampled from March to June 2005 (including the sequence originating from a traveller back from Comoros) had E1-226A. Between September and end December 2005, 21 sequences showed E1-226V. Among 17 Reunion sequences from 2006, E1-226V was observed 12 times and E1-226A 5 times (Table 1). On Madagascar and Seychelles sequences, for which the samples were collected when the first clinical cases were suspected (i.e probably at the beginning of the outbreaks), only the E1-226 Ala was observed. On Mayotte 2006 sequences, only the E1-226 V was observed. On Mauritius 2006 sequences, both E1-226 Ala and Val were observed.

[0131]To date, only CHIKV laboratory strains, passaged many times on mosquito or mammalian cells, had been entirely sequenced [9]. We provide for the first time nearly complete nucleotide sequences of six clinical isolates passaged in-vitro only once or twice (see M&M section). The presence in infected patients of a mixed viral population, called quasispecies [31-33], with genotypes co-existing in an equilibrium governed by a balance between mutation and natural selection. The presence in S27 of an Arg codon instead of the opal stop codon in Indian Ocean isolates is probably explained by numerous in-vitro passages of S27, as evolution of opal to Arg was observed experimentally in ONN viruses [23]. Whereas it may be advantageous for viral quasispecies to maintain the opal codon in-vivo, an Arg codon probably confers a selective advantage in-vitro, as observed for the closely related Semliki Forest virus [34]. Chikungunya virus quasispecies situation in-vivo could also explain the nsP1-T301I polymorphism observed for the LCR isolate 06.27. Indeed, it is likely that selection for a subset of genotypes harboring this change may be associated with invasion of the LCR [33]. These results underscore that the genome sequence of laboratory "reference" strains may not accurately reflect the natural situation, as the genotypic complexity of quasispecies in-vivo is subject to erosion by in-vitro selection. Since the Indian Ocean isolates sequenced here were subjected to in-vitro selection for only a few generations, they probably correspond more closely to the in-vivo genotypes than previously sequenced chikungunya strains.

[0132]The amino acid (aa) differences detected among the outbreak 1 isolates may relate to biological or pathogenic characteristics of the virus. Although our viral culture results are preliminary, they clearly show phenotypic differences between the unique isolate from CSF (06.27), isolated from a neonatal encephalopathy case, and three other isolates, associated with either the classical form of the disease or encephalopathy. The larger foci observed in culture with 06.27 could reflect a higher replication rate of the virus and be linked to the specific amino acid changes identified in nsP1, nsP2 and nsP3. Single amino-acid changes in nsP1, including a Thr/Ile change (residue 538 of Sindbis virus) [35, 36] and a 18-nt deletion in nsP3 have previously been shown to affect neurovirulence in other alphaviruses [35-37]. However, in the absence of nsP1 structural data, it is difficult to predict the structural or functional impact of the I301T change observed in 06.27 isolate. It should also be noted that all the viral sequences determined from either the serum or the isolates from three neonatal encephalopathy cases and an adult meningo-encephalitis case had E1-226 Val. However, as this genotype is observed also in classical forms of the disease, a potential link of E1-226 Val with neuropathogenesis needs further studies. Host factors have to be considered in the occurrence of neurological forms of the disease. For example, the blood-brain crossing may be favoured by young age or hypertension.

[0133]Unique molecular signatures of the Indian Ocean outbreak genomes were identified when they were compared to all other reported alphavirus sequences. These features represent interesting targets for future functional studies, as well as for epidemiological follow-up. One particularly interesting feature was the E1-226 Val residue (see above). Another interesting molecular signature of Indian Ocean outbreak genomes was E1-284 Asp. Although pseudo-atomic model of the scaffold used is of modest resolution (the resolution of the crystal structure is limited--approaching 3 Å--and the model results of fitting this structure into a 9 Å resolution cryo-electron microscopy reconstruction), it appears that the side-chain of Asp 284 interacts with the main chain of an adjacent E1 polypeptide in the virion. Indeed, it is in a position compatible with acceptance of a hydrogen bond from main chain amide 379 from the neighboring E1 protomer. Because the packing is very tight (see FIG. 1B), it is possible that the longer Glutamic acid side chain (which has an extra CH2 group compared to Asp or Asn) may introduce a slight distortion at the contact sites, an effect that is propagated by the icosahedral T=4 symmetry of the virion. Thus, a cooperative effect due to this change at position Asp 284 may play a role in either allowing a less efficient assembly of new particles in infected cells, or a more efficient particle disassembly process during invasion of a new cell, or a combination of both. This information 1 tion can guide new site-directed mutagenesis studies, using reverse genetics, to test the effect of the Asp/Glu replacement on the virus cycle.

Example 2

Identification and Characterization of a Soluble Form of E2 (sE2) of the CHIK Virus

[0134]The TOPO/CHIK-21.pE2 (CNCM I-3587) plasmid containing the cDNA coding for the pE2 glycoprotein (E3+E2) from the CHIK 21 virus strain (Schuffenecker et al., Plos Med., 3:1058, 2006) was used as a template for the amplification by PCR of the ectodomain sequence of the E2 envelope glycoprotein (FIG. 29). The ectodomain of gp-E2 (E2-1 to E2-364; 85% of E2) is strictly conserved among the CHIK-21, -27, 49 and 115 cell lines isolated in the Indian Ocean during the epidemic outbreak of 2005-06 (see FIG. 29). The soluble form of the sE2 corresponds to the gp-E2 ectodomain which is deleted at the carboxylic terminal of its transmembrane anchor region. It is of interest that the soluble form carries the main epitopes eliciting virus-neutralizing antibodies. The PCR primers are described in FIG. 30 (SEQ ID NO:79 and 80): they allow the cloning of the sE2 sequence between the unique sites Bg/lI and NotI of the pMT/BiP/V5-HisA vector (Invitrogen), on the one hand in a phase dependent on the BiP peptide signal at the N-terminal, and on the other hand in joining successive V5 (His)6 tags at its carboxylic terminal.

[0135]Drosophila S2 cells were transfected with the recombinant plasmid pMT/BiP/CHIK-sE2 in the presence of the plasmid coding for the blasticidin resistance gene. The S2/CHIK-sE2 stable cell line was obtained by successive passages in presence of blasticidin. The cell line was selected for its capacity to promote efficient secretion of the CHIK-sE2 virus following the activation of the metallothioneine promoter.

[0136]The S2/CHIK-sE2 cells in suspension were induced for the secretion of sE2 during 21 days in the presence of Cu₂+. The cellular supernatant is filtered at 0.22 μM and concentrated for 16 hours on an affinity column of 5 ml HiTrap Chelating HP (Amersham Biosciences) with the help of a peristaltic pump. The CHIK sE2 protein is eluded from the affinity column in the presence of increasing concentrations of imidazole (50, 100 and 500 mM, pH 8). The CHIK sE2 protein is specifically eluded at a concentration of 500 mM imidazole (E₃ elution) from the E₃₇ fraction (FIG. 31). The sE2 protein is detected as being highly purified in PAGESDS following Coomassie Blue coloration. The sE2 protein eluded in the E₃₉ fraction is specifically immunodetected by an ascite (HMAF) of a mouse hyperimmunized against the CHIK virus which was produced at the IMFH unit (FIG. 32). No cross-reactivity was observed with the anti-dengue (DEN) or anti-West Nile (WN) HMAHF and the monoclonal antibody 9D12 anti-DEN E. The soluble DEN sE proteins (DEN-3 and DEN-4) and WN sE purified from the supernatants of the S2 cellular clones induced according to the protocol described hereinabove are used as control viral antigens for the specificity of anti-CHIK murine antibodies.

Example 3

Construction of the TRIP Vector Expressing the Soluble Form of E2 (sE2) of the CHIK Virus According to the Present Invention

[0137]The gene coding the CHIK sE2 protein has been optimised by the Genecust firm so as to provide a synthetic DNA with an enriched G+C content in comparison to the cDNA obtained from the viral genomic RNA. The G+C rich codons (amino acids E2-1 to E2-364, soluble gp-E2 ectodomain, sE2) were fused to the signal peptide sequence of the human calreticuline (ssCRT) MLLSVPLLLLGLLGLAA (SEQ ID NO: 77) for translocation of the viral protein into the secretion pathway. The enzyme restriction sites BamHi in 5' and XhoI in 3' have been added at their respective ends of the sequences coding for the fusion ssCRT+sE2 protein.

[0138]The synthetic gene was cloned into the TRIP vector between the BamHI and XhoI sites under the transcription of the ieCMV promoter. The non-replicative and integrative TRIP/CHIK.sE2 plasmid thus produced was validated for the expression of the sE2 protein following transduction of 293 cells.

[0139]As shown in FIG. 33, the inventors have constructed a vector expressing the CHIK sE2. As mentioned above, the original CHIK sE2 sequence cloned into the TRIP vector has been modified for improving expression in mammalian cells (FIG. 34).

[0140]FIG. 35 shows mammalian cells, such as the 293 cells, transduced with the TRIP-CHIK.sE2 vector. The expressed sE2 protein has been revealed by IF with anti-CHIK antibodies.

Example 4

Production of Recombinant Protein sE2 and Specific Monoclonal Antibodies

[0141]The inventors have generated the stable inducible S2/CHIK.sE2 cell line which releases the soluble form of the envelope E2-glycoprotein (sE2) from Reunion CHIK virus strains. The inventors have also generated a stable cell line 293A/CHIK.sE2 which was transducted by the recombinant lentiviral vector TRIP/CHIK.sE2. A synthetic sE2 gene that was modified for optimal codon usage in mammalian cells had to be used in order to obtain efficient expression of CHIK virus sE2 in human fibroblastic 293A cells. The TRIP/CHIK.sE2 vector is currently assessed for its capability to induce protective immunity in a murine model of experimental infection. Viral suspension mainly enriched in CHIK pE2 (E2 precursor or E3E2) was obtained by solubilizing CHIK virions grown in mosquito cells with Triton X-100. Adult mice were hyperimmunized with CHIK pE2 in the presence of adjuvant in order to generate hybridoma directed against CHIK structural proteins. Anti-CHIK E2 monoclonal antibodies produced by mouse hybridoma were characterized by ELISA assay on highly purified CHIK virion and Western blot on secreted sE2 from stable cell line S2/CHIK.sE2. (FIGS. 50, 51 and Table 9). Fluorescent immunodetection assays of intracellular or surface viral antigens were also established on CHIK virus-infected VERO cells and stable 293A/CHIK.sE2 transduced cell line (FIGS. 52-55). Anti-CHIK.sE2 MAbs of the inventors find a potential use in developing early viral diagnosis of CHIK disease based on immunocapture of CHIK virions in viremic blood of patients, and as tools for immunological as well as virological studies.

TABLE-US-00001 TABLE 1 Characteristics of the patients Patients Region or Sampling Virus Isolate No. Island Island Town or Locality Sample (b) Date Clinical signs (c) No. (d) E1-226 (e) 1 Reunion -- -- S 16-Mar-05 Classical 05.61 (G) A (*) (Comoros) (a) 2 Reunion West St Gilles Les Bains S 11-Apr-05 Classical 05.55 A (*) 3 Reunion South Saint Pierre S 2-May-05 Classical 05.107 A (*) 4 Reunion West Mare SeCilaos S 4-May-05 Classical 05.111 A (*) 5 Reunion South La Rivieve St Louis S 6-May-05 Classical 05.115 (G) A (*) 6 Reunion South St Louis CSF 7-Sep-05 Neonatal 05.223 V (**) encephalopathy 7 Reunion South La Rivieve St Louis S 11-Oct-05 Classical 06.55 V (**) 8 Reunion South St Louis S 21-Oct-05 Classical 06.59 V (**) 9 Reunion South La Rivieve St Louis S 21-Oct-05 Classical 06.53 V (**) 10 Reunion South La Rivieve St Louis P 26-Oct-05 Classical n.i. V (**) 11 Reunion South St Joseph P 9-Nov-05 Classical n.i. V (**) 12 Reunion South La Rivieve St Louis P 10-Nov-05 Classical n.i. V (**) 13 Reunion South St Louis P 20-Nov-05 Classical n.i. V (**) 14 Reunion South La Rivieve St Louis P 21-Nov-05 Classical n.i. V (**) 15 Reunion South La Rivieve St Louis S 23-Nov-05 Classical 06.45 V (**) 16 Reunion South La Rivieve St Louis S 28-Nov-05 Neonatal ME 06.21 (G) V (***) (parents) 17 Reunion South St Joseph S 23-Nov-05 Classical 06.47 V (**) 18 Reunion South La Rivieve St Louis P 24-Nov-05 Classical n.i. V (**) 19 Reunion South Le Tampon P 26-Nov-05 Classical n.i. V (**) 20 Reunion South Ravine des Cabris P 25-Nov-05 Classical n.i. V (**) 21 Reunion South St Joseph (parents) S 29-Nov-05 Neonatal ME 06.25 V (**) 21 Reunion South St Joseph (parents) CSF 29-Nov-05 Neonatal ME 06.27 (G) V (***) 22 Reunion South St Louis S 2-Dec-05 Classical 06.49 (G) V (***) 23 Reunion South St Louis P 8-Dec-05 Classical n.i. V (**) 24 Reunion South Ravine des Cabris S 9-Dec-05 ME 06.17 V (**) 25 Reunion South St Louis P 13-Dec-05 Classical n.i. V (**) 26 Reunion South St Pierre P 2-Jan-06 Classical n.i. A (**) 27 Reunion South St Pierre P 4-Jan-06 Algic symdrome n.i. A (**) 28 Reunion East St Andre S 4-Jan-06 Classical n.i. A (**) 29 Reunion South St Louis P 29-Dec-05 Algic syndrome n.i. V (**) 29 Reunion South St Louis CSF 29-Dec-05 Algic syndrome n.i. V (**) 30 Reunion South La Rivieve St Louis P 29-Dec-05 Classical n.i. V (**) 31 Reunion South La Rivieve St Louis P 27-Dec-05 Classical n.i. V (**) 32 Reunion South St Pierre P 27-Dec-05 Severe vesicular n.i. V (**) rash lower limbs 32 Reunion South St Pierre L 28-Dec-05 Severe vesicular n.i. V (**) rash lower limbs 33 Reunion South Ravine des Cabris P 4-Jan-06 n.d. n.i. A (**) 34 Reunion South St Joseph P 3-Jan-06 Algic syndrome n.i. V (**) 35 Reunion South St Louis P 2-Jan-06 Algic syndrome n.i. V (**) 36 Reunion South St Joseph P 5-Jan-06 Algic syndrome n.i. To be determined 37 Reunion South Ravine des Cabris P 6-Jan-06 Classical n.i. V (**) 38 Reunion South St Louis P 6-Jan-06 Algic syndrome n.i. V (**) 39 Reunion West Saint-Paul hospital S 5-Jan-06 n.d. n.i. A (**) 40 Reunion West St Leu S 19-Jan-06 Classical n.i. V (**) 41 Reunion South Les Avirons S 30-Jan-06 Classical 06.97 V (**) 42 Reunion East St Benoit S 3-Feb-06 Hepatitis n.i. V (**) 43 Reunion n.d. n.d. S 22-Feb-06 Classical n.i. V (**) 44 Seychelles Mahe Anse aux Pins S 9-Aug-05 Classical 05.209 (G) A (*) island 45 Seychelles Mahe Anse aux Pins S 10-Aug-05 Classical negative A (**) island 46 Seychelles Mahe Anse aux Pins S 10-Aug-05 Classical negative A (**) island 47 Madagascar East Toamasina S 1-Feb-06 Classical 06.103 A (**) 48 Madagascar East Toamasina S 8-Feb-06 Classical 06.99 A (**) 49 Madagascar East Toamasina S 9-Feb-06 Classical 06.101 A (**) 50 Madagascar East Toamasina S 15-Feb-06 Classical n.i. A (**) 51 Madagascar North Ampany S 14-Feb-06 Classical n.i. A (**) 52 Madagascar North Djamandjary S 14-Feb-06 Classical n.i. A (**) 53 Madagascar North Djamandjary S 15-Feb-06 Classical n.i. A (**) 54 Mayotte n.d. n.d. S 7-Feb-06 Classical 06.111 To be determined 55 Mayotte n.d. n.d. S 11-Feb-06 Classical n.i. V (**) 56 Mayotte n.d. n.d. S 13-Feb-06 Classical n.i. V (**) 57 Mayotte n.d. n.d. S 13-Feb-06 Classical n.i. V (**) 58 Mauritius n.d. n.d. S 12-Feb-06 Classical 06.93 V (*) 59 Mauritius n.d. n.d. S 27-Feb-06 Classical n.i. A (**) 60 Mauritius n.d. n.d. S 1-Mar-06 Classical n.i. A (**) (a) This patent traveled back from Comoros and is believed to have been infected there. (b) S: serum; P: plasma; CSF: cerebrospinal fluid (c) ME: meningo-encephalitis (d) Isolates labeled with (G) correspond to those for which the nearly complete genome sequence was established (e) A: Alanine; V: Valine; (*): Sequence determined from virus isolates; (**): Sequence determined from biological samples; (***): Sequence determined from both virus isolates and biological samples n.i.: isolation of virus not intended; n.d.: not determined

TABLE-US-00002 TABLE 2 Relevant amino acid changes identified between Indian Ocean isolates versus a selection of Alphavirus sequences. Non-structural proteins Protein nsP1 nsP1 nsP2 nsP2 nsP2 nsP2 nsP3 nsP3 nsP3 nsP3 nsP3 nsP4 Polypeptide 301 488 589 909 1177 1328 1550 1670 1691 1793 1804 1938 position (a) Protein 301 488 54 374 642 793 217 337 358 460 471 75 position (a) 05.115 T R N Y Y V H I S E S A (Genotype 1) 06.21 T R N Y Y V H I S Nd nd A (Genotype 2) 06.27 I R N Y N V H I S Del S A (Genotype 3) 06.49 T R N Y Y V H I S E S A (Genotype 4) 05.209 T R N Y Y V H I P E S A (Genotype 5) S27 T Q S H C A Y T S L P T Ross T Q S H C A Y T S L P T 37997 T K S H Y A Y T S P P T (West-African phylogroup) Nagpur (Asian nd nd nd nd nd nd nd nd nd Nd nd nd phylogroup) ONNV S Q S N H A Y ** S ** ** T EEV S Q S N E R N ** ** ** ** I SFV V S N H Y A L ** S ** ** T RRV V N S H Y G S ** ** ** ** V SINV V M S H E R K ** ** ** ** I Non-struc- tural proteins Structural proteins Protein nsP4 nsP4 E2 E2 E2 E2 E2 6K E1 E1 E1 Polypeptide 2117 2363 471 489 637 700 711 756 1035 1078 1093 position (a) Protein 254 500 146 164 312 375 386 8 226 269 284 position (a) 05.115 A L Q T M T A I A V E (Genotype 1) 06.21 A L Q T M T A I V V E (Genotype 2) 06.27 A L Q T M T A I V V E (Genotype 3) 06.49 A L Q T M T A I V V E (Genotype 4) 05.209 A L R T M T A I A V E (Genotype 5) S27 T Q Q A T S V I A M D Ross T Q Q A T S V V A M D 37997 T Q Q A T S V A A V D (West-African phylogroup) Nagpur (Asian nd nd Q A T S G V A M D phylogroup) ONNV T E H A* T S L* T* A V D EEV V E E G* S A T* D* A E D SFV T E H V* T S C* A* P M D RRV T E H D* D S C* A* P M D SINV T E V A* V T V* S* A V N (a) S27 reference numbering *Variable position, ** Hypervariable position ONV: o'nyong-nyong virus; SFV: Semliki Forest virus; RRV: Ross River virus; SINV: Sindbis virus; EEV: Eastern-Equine Encephalitis virus. nd: not determined. Note that the opal stop codon observed in nsP3-524 of Indian Ocean outbreak isolates, but not in S27, is not represented in the Table.

TABLE-US-00003 TABLE 3 Polymorphisms observed among Indian Ocean isolates Genome position (b) 978 1378 3605 4705 5147 5452 5453-5455 Protein nsP1 nsP1 nsP2 nsP3 nsP3 nsP3 nsP3 Protein position (for aa change) 301 -- 642 -- 358 -- 460 05.115 (Genotype 1) C G T T T G GAA (Glu) 05.61 (Genotype 1) C G T T T n.d. n.d. 06.21 (Genotype 2) C G T T T G GAA (Glu) 06.27 (Genotype 3) T (Thr→Ile) G A (Tyr→Asn) A T A Deleted 06.49 (Genotype 4) C A T T T G GAA (Glu) 05.209 (Genotype 5) C G T T C (Ser→Pro) G GAA (Glu) S27 (a) C G T T T G GAA (Glu) Genome position (b) 6547 7045 8978 9600 10670 11295 11421 Protein nsP4 nsP4 E2 E2 E1 E1 3'NTR Protein position (for aa change) -- -- 146 -- 226 -- -- 05.115 (Genotype 1) G C A T C G C 05.61 (Genotype 1) G C A T C G C 06.21 (Genotype 2) G C A T T (Ala→Val) G C 06.27 (Genotype 3) A C A T T (Ala→Val) G C 06.49 (Genotype 4) A C A C T (Ala→Val) G T 05.209 (Genotype 5) G T G (Gln→Arg) T C A C S27 (a) G C A T C G C (a) Only sites that are variable among Indian Ocean outbreak isolates are represented; those sites that were distinct between Indian Ocean outbreak isolates and other viruses are given as Supplementary Information (b) S27 numbering

TABLE-US-00004 TABLE 4 Primers used for RT-PCR and sequencing SEQ ID Fragment Gene Primer (a) sequence (5' to 3') NO. FG1 5'NC 18F CACGTAGCCTACCAGTTTCTTA 35 nsP1 871R ATGGAACACCGATGGTAGGTG 36 FG2 nsP1 616F AACCCCGTTCATGTACAATGC 37 nsP1 1435R CGGTACCACAAAGCTGTCAAAC 38 FG3 nsP1 1317F CACTGACCTGGTGCTGTCTATG 39 nsP2 2130R AGTCCTGCAGCTTCTTCCTTC 40 FG4 nsP1 1412F CGAGTTTGACAGCTTTGTGGTA 41 nsP2 2227R ATGACTGCAATTTTGTATGGGC 42 FG5 nsP2 1908F CAATCTCGCCTGAAGACTTCC 43 nsP2 2709R TCCACTACAATCGGCTTGTTG 44 FG6 nsP2 2530F GTGCGGCTTCTTCAATATGATG 45 nsP2 3343R TCCAGGCCTATTATCCCAGTG 46 FG7 nsP2 2577F AACATCTGCACCCAAGTGTACC 47 nsP2 3504R GTCTCCTGTTGGCCGGTATAAT 48 FG8 nsP2 3332F TAATAGGCCTGGAGGGAAGATG 49 nsP3 4134R CTACGCACTCTTCATCGTTCTT 50 FG9 nsP2 3885F GAACGAGTCATCTGCGTATTGG 51 nsP3 4725R ATATCTCTGCCATATCCACTGC 52 FG10 nsP3 4458F TCTTTACAGCCATGGACTCGAC 53 nsP3 5273R CGACAGGTACGGTGCTCATTAC 54 FG11 nsP3 5065F TGTACAGGAAGCGAGTACGACC 55 nsP4 5874R TCTACTTTGCGCGACTGATACC 56 FG12 nsP4 5630F ACGGACGACGAGTTACGACTAG 57 nsP4 6380R CCCAGTATTCTTGGTTGCATG 58 FG13 nsP4 6184F AAAACAGCACGCTTACCACG 59 nsP4 6936R AACTTGAAGCGCGTACCTGTC 60 FG14 nsP4 6732F TCATAGCCGCACACTTTAAGC 61 nsP4 7495R AGGACCGCCGTACAAAGTTAC 62 FG15 nsP4 7278F GCAGGTGACGAACAAGATGAG 63 C 8034R CCGCTTAAAGGCCAATTTG 64 FG16 C 7910F TCGAAGTCAAGCACGAAGG 65 E2 8670R GTCTGTCGCTTCATTTCTGATG 66 FG17 E3 8459F TGCTTGAGGACAACGTCATGAG 67 E2 9240R TTTGTGATTGGTGACCGCG 68 FG18 E2 9093F AGTCCGGCAACGTAAAGATCAC 69 6K 9861R AAAGGTTGCTGCTCGTTCCAC 70 FG19 E2 9648F AGTTGTGTCAGTGGCCTCGTTC 71 E1 10403R TAAAGGACGCGGAGCTTAGCTG 72 FG20 E1 10145F ACAAAACCGTCATCCCGTCTC 73 E1 11158R TGACTATGTGGTCCTTCGGAGG 74 FG21 E1 10959F CAGCAAGAAAGGCAAGTGTGC 75 3'NC 11770R TTTGCCAATTATGGTATTCA 76 (a) The primer name indicates their position and direction on the nucleotide sequence of the S27 genome.

TABLE-US-00005 TABLE 5 Amino-acid changes observed between strain S27 and Indian Ocean outbreak strains in the non-structural proteins nsP1 and nsP2 Protein ##STR00001## ##STR00002## ##STR00003## ##STR00004## ##STR00005## ##STR00006## ##STR00007## ##STR00008## nsP2 nsP2 nsP2 nsP2 nsP2 Protein 172 234 301 383 384 481 488 507 54 374 642 643 793 position Polypeptide 172 234 301 383 384 481 488 507 589 909 1177 1178 1328 position S27 L E T M I T Q L S H C S A 05.115 V K T L L I R R N Y Y N V 05.61 V K T L L I R R N Y Y N V 06.21 V K T L L I R R N Y Y N V 06.27 V K I L L I R R N Y N N V 06.49 V K T L L I R R N Y Y N V 05.209 V K T L L I R R N Y Y N V nsP3 and nsP4 Protein nsP3 nsP3 nsP3 nsP3 nsP3 nsP3 nsP3 nsP3 nsP3 nsP3 nsP3 nsP3 nsP3 Protein 175 217 326 331 337 352 358 376 382 460 461 462 471 position Polypeptide 1508 1550 1659 1664 1670 1685 1691 1709 1715 1793 1794 1795 1804 position S27 V Y P V T K S I A L L S P 05.115 I H S A I E S T T E P N S 05.61 I H S A I E S T T nd nd nd nd 06.21 I H S A I E S T T E P N S 06.27 I H S A I E S T T del P N S 06.49 I H S A I E S T T E P N S 05.209 I H S A I E P T T E P N S Protein nsP3 nsP4 nsP4 nsP4 nsP4 nsP4 nsP4 Protein 524 75 254 500 514 555 604 position Polypeptide 1857 1938 2117 2363 2377 2418 2467 position S27 R T T Q I V V 05.115 STOP A A L T I I 05.61 nd A A L T I I 06.21 STOP A A L T I I 06.27 STOP A A L T I I 06.49 STOP A A L T I I 05.209 STOP A A L T I I Grayed cells correspond to aa that were variable among Indian Ocean outbreak isolates

TABLE-US-00006 TABLE 6 Amino-acid changes in the structural genes among S27, Ross and Indian Ocean outbreak strains. ##STR00009## (a): When two nt positions were variable in the same codon, only the postion of the upstream nt is given Grayed cells correspond to amino acid changes among Indian Ocean outbreak isolates.

TABLE-US-00007 TABLE 7 Sequence used for the phylogenetic analysis of partial E1 sequences Genomic Isolation Accession No. Strain domain Strain Origin Date Phylogroup Reference AF192906 CAR 256 E1 partial Central African Region Unknown Central Africa 1 AF192907 Ag41855 E1 partial Uganda 1982 Central Africa 1 AY549583 ChikRCA E1 partial DRC (b) 1996 Central Africa 2 AF192903 AR 18211 E1 partial South African Republic 1976 Central-East/South Africa 1 AF192904 SA H2123 E1 partial South African Republic 1976 Central-East/South Africa 1 AF192905 Ross E1 partial Tanzanie 1953 Central-East/South Africa 1 AF490259 Ross Complete Tanzanie 1953 Central-East/South Africa na genome AF369024 S27 Complete Tanzanie 1952 Central-East/South Africa 3 genome AY549576 DRC010 E1 partial DRC (b) 2000 Central Africa 2 AY549577 DRC027 E1 partial DRC (b) 2000 Central Africa 2 AY549579 DRC1719 E1 partial DRC (b) 2000 Central Africa 2 AY549575 DRC007 E1 partial DRC (b) 2000 Central Africa 2 AY549578 DRC1718 E1 partial DRC (b) 2000 Central Africa 2 AY549581 DRC1725 E1 partial DRC (b) 2000 Central Africa 2 AY549582 DRC1728 E1 partial DRC (b) 2000 Central Africa 2 AY549580 DRC1720 E1 partial DRC (b) 2000 Central Africa 2 AY549584 DRC1730 E1 partial DRC (b) 2000 Central Africa 2 AF192896 644188 E1 partial Thailand 1988 Asian 1 AF192899 3412/78 E1 partial Thailand 1978 Asian 1 AF192894 RSU1 E1 partial Indonesia 1985 Asian 1 AF192895 H15483 E1 partial Philippines 1985 Asian 1 AF192898 1455/75 E1 partial Thailand 1975 Asian 1 AF192901 Gibbs 63-263 E1 partial India 1963 Asian 1 AF192902 PO731460 E1 partial India 1973 Asian 1 AF192897 C-03295 E1 partial Thailand 1995 Asian 1 AF192900 SV045196 E1 partial Thailand 1996 Asian 1 L37661 Vaccine strain polyprotein Na na Asian na gene AF192892 37997 E1 partial Na na West African 1 AY726732 37997 Complete Senegal 1983 West African 4 genome AF192891 PM2951 E1 partial Senegal 1966 West African 1 AF192893 IbH35 E1 E1 partial Nigeria 1964 West African 1 References: (1) Powers et al., Pastorino et al., 2004; (3) Khan et al., 2002; (4) Vantandingham et al., 2005. (b) Democratic Republic of the Congo

TABLE-US-00008 TABLE 8 Sequence percent similarity based on amino acids and nucleotides (in parentheses) for the structural (SP) and non-structural (NSP) proteins of selected Alphaviruses. 05.115/06.49 05.115 06.49 Virus Strain Accession No. NSP SP SP CHIKV 05.115 To be submitted 100 (100) 100 (100) -- 06.49 To be submitted 100 (99.97) 99.91 (99.95) 100 (100) S27 AF369024 98.79 (97.3) 98.47 (97.34) 98.38 (97.33) 37997 AY726732 95.88 (85.5) 95.82 (84.87) 95.74 (84.81) Nagpur AY424803 NA 97.18 (94.85) 97.10 (94.79) Vaccine L37661 NA 96.92 (94.24) 96.83 (94.19) ONNV Gulu M20303 85.90 87.30 87.22 SFV 42S RNA genome X04129 70.55 65.20 65.20 RRV NB5092 M20162 69.66 64.40 64.40 SINV HRSP J02363 59.25 47.40 47.31 CHIKV: chikungunya virus; ONNV: o'nyong-nyong virus; SFV: Semliki Forest virus; RRV: Ross River virus; SINV: Sindbis virus NA: Not Available.

TABLE-US-00009 TABLE 9 List of biological assays performed to validate the reactivity of anti-CHIK E2 MAbs BIOLOGICAL ASSAYS ELISA on solubilized antigens from CHIK virions ELISA on purified CHIK virions (La Reunion IsI.) ELISA on purified CHIK virions (+TX-100) ELISA on purified CHIK virions (+NP-40) IF assay on CHIKV-infected VERO cells FACS analysis on cell surface of CHIKV-infected VERO cells Western blot on recombinant CHIK sE2 from S2 cells IF assay on stable TRIP/CHIK.sE2-transduced 293A cell clone Western blot on recombinant CHIK sE2 from TRIP/CHIK.sE2-transduced 293A cell clone

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Sequence CWU 1

103111601DNAChikungunya virus 1caaagcaaga gattaataac ccatcatgga tcctgtgtac gtggacatag acgctgacag 60cgcctttttg aaggccctgc aacgtgcgta ccccatgttt gaggtggaac caaggcaggt 120cacaccgaat gaccatgcta atgctagagc gttctcgcat ctagctataa aactaataga 180gcaggaaatt gaccccgact caaccatcct ggatatcggc agtgcgccag caaggaggat 240gatgtcggac aggaagtacc actgcgtctg cccgatgcgc agtgcggaag atcccgagag 300actcgccaat tatgcgagaa agctagcatc tgccgcagga aaagtcctgg acagaaacat 360ctctggaaag atcggggact tacaagcagt aatggccgtg ccagacacgg agacgccaac 420attctgctta cacacagacg tctcatgtag acagagagca gacgtcgcta tataccaaga 480cgtctatgct gtacacgcac ccacgtcgct ataccaccag gcgattaaag gggtccgagt 540ggcgtactgg gttgggttcg acacaacccc gttcatgtac aatgccatgg cgggtgccta 600cccctcatac tcgacaaact gggcagatga gcaggtactg aaggctaaga acataggatt 660atgttcaaca gacctgacgg aaggtagacg aggcaagttg tctattatga gagggaaaaa 720gctaaaaccg tgcgaccgtg tgctgttctc agtagggtca acgctctacc cggaaagccg 780caagctactt aagagctggc acctgccatc ggtgttccat ttaaagggca aactcagctt 840cacatgccgc tgtgatacag tggtttcgtg tgagggctac gtcgttaaga gaataacgat 900gagcccaggc ctttatggaa aaaccacagg gtatgcggta acccaccacg cagacggatt 960cctgatgtgc aagactaccg acacggttga cggcgaaaga gtgtcattct cggtgtgcac 1020atacgtgccg gcgaccattt gtgatcaaat gaccggcatc cttgctacag aagtcacgcc 1080ggaggatgca cagaagctgt tggtggggct gaaccagaga atagtggtta acggcagaac 1140gcaacggaat acgaacacca tgaaaaatta tctgcttccc gtggtcgccc aagccttcag 1200taagtgggca aaggagtgcc ggaaagacat ggaagatgaa aaactcctgg gggtcagaga 1260aagaacactg acctgctgct gtctatgggc attcaagaag cagaaaacac acacggtcta 1320caagaggcct gatacccagt caattcagaa ggttcaggcc gagtttgaca gctttgtggt 1380accgagtctg tggtcgtccg ggttgtcaat ccctttgagg actagaatca aatggttgtt 1440aagcaaggtg ccaaaaaccg acctgatccc atacagcgga gacgcccgag aagcccggga 1500cgcagaaaaa gaagcagagg aagaacgaga agcagaactg actcgcgaag ccctaccacc 1560tctacaggca gcacaggaag atgttcaggt cgaaatcgac gtggaacagc ttgaggacag 1620agcgggcgca ggaataatag agactccgag aggagctatc aaagttactg cccaaccaac 1680agaccacgtc gtgggagagt acctggtact ctccccgcag accgtactac gtagccagaa 1740gctcagtctg attcacgctt tggcggagca agtgaagacg tgcacgcaca acggacgagc 1800agggaggtat gcggtcgaag cgtacgacgg ccgagtccta gtgccctcag gctatgcaat 1860ctcgcctgaa gacttccaga gtctaagcga aagcgcaacg atggtgtata acgaaagaga 1920gttcgtaaac agaaagctac accatattgc gatgcacgga ccagccctga acaccgacga 1980agagtcgtat gagctggtga gggcagagag gacagaacac gagtacgtct acgacgtgga 2040tcagagaaga tgctgtaaga aggaagaagc cgcaggactg gtactggtgg gcgacttgac 2100taatccgccc taccacgaat tcgcatatga agggctaaaa atccgccctg cctgcccata 2160caaaattgca gtcataggag tcttcggagt accgggatct ggcaagtcag ctattatcaa 2220gaacctagtt accaggcagg acctggtgac tagcggaaag aaagaaaact gccaagaaat 2280caccaccgac gtgatgagac agagaggtct agagatatct gcacgtacgg ttgactcgct 2340gctcttgaat ggatgcaaca gaccagtcga cgtgttgtac gtagacgagg cgtttgcgtg 2400ccactctgga acgctacttg ctttgatcgc cttggtgaga ccaaggcaga aagttgtact 2460ttgtggtgac ccgaagcagt gcggcttctt caatatgatg cagatgaaag tcaactataa 2520tcacaacatc tgcacccaag tgtaccacaa aagtatctcc aggcggtgta cactgcctgt 2580gaccgccatt gtgtcatcgt tgcattacga aggcaaaatg cgcactacga atgagtacaa 2640caagccgatt gtagtggaca ctacaggctc aacaaaacct gaccctggag acctcgtgtt 2700aacgtgcttc agagggtggg ttaaacaact gcaaattgac tatcgtggat acgaggtcat 2760gacagcagcc gcatcccaag ggttaaccag aaaaggagtt tacgcagtta gacaaaaagt 2820taatgaaaac ccgctctatg catcaacgtc agagcacgtc aacgtactcc taacgcgtac 2880ggaaggtaaa ctggtatgga agacactttc cggcgacccg tggataaaga cgctgcagaa 2940cccaccgaaa ggaaacttca aagcaactat taaggagtgg gaggtggagc atgcatcaat 3000aatggcgggc atctgcagtc accaaatgac cttcgataca ttccaaaata aagccaacgt 3060ttgttgggct aagagcttgg tccctatcct cgaaacagcg gggataaaac taaatgatag 3120gcagtggtct cagataattc aagccttcaa agaagacaaa gcatactcac ctgaagtagc 3180cctgaatgaa atatgtacgc gcatgtatgg ggtggatcta gacagcgggc tattttctaa 3240accgttggtg tctgtgtatt acgcggataa ccactgggat aataggcctg gagggaaaat 3300gttcggattt aaccccgagg cagcatccat tctagaaaga aagtatccat tcacaaaagg 3360gaagtggaac atcaacaagc agatctgcgt gactaccagg aggatagaag actttaaccc 3420taccaccaac atcataccgg ccaacaggag actaccacac tcattagtgg ccgaacaccg 3480cccagtaaaa ggggaaagaa tggaatggct ggttaacaag ataaacggcc accacgtgct 3540cctggtcagt ggctataacc ttgcactgcc tactaagaga gtcacttggg tagcgccgtt 3600aggtgtccgc ggagcggact acacatacaa cctagagttg ggtctgccag caacgcttgg 3660taggtatgac ctagtggtca taaacatcca cacacctttt cgcatacacc attaccaaca 3720gtgcgtcgac cacgcaatga aactgcaaat gctcgggggt gactcattga gactgctcaa 3780accgggcggc tctctattga tcagagcata tggttacgca gatagaacca gtgaacgagt 3840catctgcgta ttgggacgca agtttagatc gtctagagcg ttgaaaccac catgtgtcac 3900cagcaacact gagatgtttt tcctattcag caactttgac aatggcagaa ggaatttcac 3960aactcatgtc atgaacaatc aactgaatgc agccttcgta ggacaggtca cccgagcagg 4020atgtgcaccg tcgtaccggg taaaacgcat ggacatcgcg aagaacgatg aagagtgcgt 4080agtcaacgcc gctaaccctc gcgggttacc gggtgacggt gtttgcaagg cagtatacaa 4140aaaatggccg gagtccttta agaacagtgc aacaccagtg ggaaccgcaa aaacagttat 4200gtgcggtacg tatccagtaa tccacgctgt tggaccaaac ttctctaatt attcggagtc 4260tgaaggggac cgggaattgg cagctgccta tcgagaagtc gcaaaggaag taactaggct 4320gggagtaaat agtgtagcta tacctctcct ctccacaggt gtatactcag gagggaaaga 4380caggctgacc cagtcactga accacctctt tacagccatg gactcgacgg atgcagacgt 4440ggtcatctac tgccgcgaca aagaatggga gaagaaaata tctgaggcca tacagatgcg 4500gacccaagta gagctgctgg atgagcacat ctccatagac tgcgatattg ttcgcgtgca 4560ccctgacagc agcttggcag gcagaaaagg atacagcacc acggaaggcg cactgtactc 4620atatctagaa gggacccgtt ttcatcagac ggctgtggat atggcggaga tacatactat 4680gtggccaaag caaacagagg ccaatgagca agtctgccta tatgccctgg gggaaagtat 4740tgaatcgatc aggcagaaat gcccggtgga tgatgcagac gcatcatctc cccccaaaac 4800tgtcccgtgc ctttgccgtt acgctatgac tccagaacgc gtcacccggc ttcgcatgaa 4860ccacgtcaca agcataattg tgtgttcttc gtttcccctc ccaaagtaca aaatagaagg 4920agtgcaaaaa gtcaaatgct ctaaggtaat gctatttgac cacaacgtgc catcgcgcgt 4980aagtccaagg gaatatagat cttcccagga gtctgcacag gaggcgagta caatcacgtc 5040actgacgcat agtcaattcg acctaagcgt tgatggcgag atactgcccg tcccgtcaga 5100cctggatgct gacgccccag ccctagaacc agcactagac gacggggcga cacacacgct 5160gccatccaca accggaaacc ttgcggccgt gtctgattgg gtaatgagca ccgtacctgt 5220cgcgccgccc agaagaaggc gagggagaaa cctgactgtg acatgtgacg agagagaagg 5280gaatataaca cccatggcta gcgtccgatt ctttagggca gagctgtgtc cggtcgtaca 5340agaaacagcg gagacgcgtg acacagcaat gtctcttcag gcaccaccga gtaccgccac 5400ggaaccgaat catccgccga tctccttcgg agcatcaagc gagacgttcc ccattacatt 5460tggggacttc aacgaaggag aaatcgaaag cttgtcttct gagctactaa ctttcggaga 5520cttcttacca ggagaagtgg atgacttgac agacagcgac tggtccacgt gctcagacac 5580ggacgacgag ttatgactag acagggcagg tgggtatata ttctcgtcgg acaccggtcc 5640aggtcattta caacagaagt cagtacgcca gtcagtgctg ccggtgaaca ccctggagga 5700agtccacgag gagaagtgtt acccacctaa gctggatgaa gcaaaggagc aactattact 5760taagaaactc caggagagtg catccatggc caacagaagc aggtatcagt cgcgcaaagt 5820agaaaacatg aaagcagcaa tcatccagag actaaagaga ggctgtagac tatacttaat 5880gtcagagacc ccaaaagtcc ctacttaccg gactacatat ccggcgcctg tgtactcgcc 5940tccgatcaac gtccgattgt ccaatcccga gtccgcagtg gcagcatgca atgagttctt 6000agctagaaac tatccaactg tctcatcata ccaaattacc gacgagtatg atgcatatct 6060agacatggtg gacgggtcgg agagttgcct ggaccgagcg acattcaatc cgtcaaaact 6120caggagctac ccgaaacagc acgcttacca cgcgccctcc atcagaagcg ctgtaccgtc 6180cccattccag aacacactac agaatgtact ggcagcagcc acgaaaagaa actgcaacgt 6240cacacagatg agggaattac ccactttgga ctcagcagta ttcaacgtgg agtgtttcaa 6300aaaattcgca tgcaaccaag aatactggga agaatttgct gccagcccta ttaggataac 6360aactgagaat ttagcaacct atgttactaa actaaaaggg ccaaaagcag cagcgctatt 6420cgcaaaaacc cataatctac tgccactaca ggaagtacca atggataggt tcacagtaga 6480tatgaaaagg gacgtgaagg tgactcctgg tacaaagcat acagaggaaa gacctaaggt 6540gcaggttata caggcggctg aacccttggc gacagcatac ctatgtggga ttcacagaga 6600gctggttagg aggctgaacg ccgtcctcct acccaatgta catacactat ttgacatgtc 6660tgccgaggat ttcgatgcca tcatagccgc acactttaag ccaggagaca ctgttttgga 6720aacggacata gcctcctttg ataagagcca agatgattca cttgcgctta ctgctttgat 6780gctgttagag gatttagggg tggatcactc cctgctggac ttgatagagg ctgctttcgg 6840agagatttcc agctgtcacc taccgacagg tacgcgcttc aagttcggcg ccatgatgaa 6900atcaggtatg ttcctaactc tgttcgtcaa cacattgtta aacatcacca tcgccagccg 6960agtgctggaa gatcgtctga caaaatccgc gtgcgcggcc ttcatcggcg acgacaacat 7020aatacatgga gtcgtctccg atgaattgat ggcagccaga tgtgccactt ggatgaacat 7080ggaagtgaag atcatagatg cagttgtatc cttgaaagcc ccttactttt gtggagggtt 7140tatactgcac gatactgtga caggaacagc ttgcagagtg gcagacccgc taaaaaggct 7200ttttaaactg ggcaaaccgc tagcggcagg tgacgaacaa gatgaagata gaagacgagc 7260gctggctgac gaagtgatca gatggcaacg aacagggcta attgatgagc tggagaaagc 7320ggtatactct aggtacgaag tgcagggtat atcagttgtg gtaatgtcca tggccacctt 7380tgcaagctcc agatccaact tcgagaagct cagaggaccc gtcataactt tgtacggcgg 7440tcctaaatag gtacgcacta cagctaccta ttttgcagaa gccgacagca agtatctaaa 7500cactaatcag ctacaatgga gttcatccca acccaaactt tttacaatag gaggtaccag 7560cctcgaccct ggactccgcg ccctactatc caagtcatca ggcccagacc gcgccctcag 7620aggcaagctg ggcaacttgc ccagctgatc tcagcagtta ataaactgac aatgcgcgcg 7680gtaccccaac agaagccacg caggaatcgg aagaataaga agcaaaagca aaaacaacag 7740gcgccacaaa acaacacaaa tcaaaagaag cagccaccta aaaagaaacc ggctcaaaag 7800aaaaagaagc cgggccgcag agagaggatg tgcatgaaaa tcgaaaatga ttgtattttc 7860gaagtcaagc acgaaggtaa ggtaacaggt tacgcgtgcc tggtggggga caaagtaatg 7920aaaccagcac acgtaaaggg gaccatcgat aacgcggacc tggccaaact ggcctttaag 7980cggtcatcta agtatgacct tgaatgcgcg cagatacccg tgcacatgaa gtccgacgct 8040tcgaagttca cccatgagaa accggagggg tactacaact ggcaccacgg agcagtacag 8100tactcaggag gccggttcac catccctaca ggtgctggca aaccagggga cagcggcaga 8160ccgatcttcg acaacaaggg acgcgtggtg gccatagtct taggaggagc taatgaagga 8220gcccgtacag ccctctcggt ggtgacctgg aataaagaca ttgtcactaa aatcaccccc 8280gagggggccg aagagtggag tcttgccatc ccagttatgt gcctgttggc aaacaccacg 8340ttcccctgct cccagccccc ttgcacgccc tgctgctacg aaaaggaacc ggaggaaacc 8400ctacgcatgc ttgaggacaa cgtcatgaga cctgggtact atcagctgct acaagcatcc 8460ttaacatgtt ctccccaccg ccagcgacgc agcaccaagg acaacttcaa tgtctataaa 8520gccacaagac catacttagc tcactgtccc gactgtggag aagggcactc gtgccatagt 8580cccgtagcac tagaacgcat cagaaatgaa gcgacagacg ggacgctgaa aatccaggtc 8640tccttgcaaa tcggaataaa gacggatgac agccacgatt ggaccaagct gcgttatatg 8700gacaaccaca tgccagcaga cgcagagagg gcggggctat ttgtaagaac atcagcaccg 8760tgtacgatta ctggaacaat gggacacttc atcctggccc gatgtccaaa aggggaaact 8820ctgacggtgg gattcactga cagtaggaag attagtcact catgtacgca cccatttcac 8880cacgaccctc ctgtgatagg tcgggaaaaa ttccattccc gaccgcagca cggtaaagag 8940ctaccttgca gcacgtacgt gcagagcacc gccgcaacta ccgaggagat agaggtacac 9000atgcccccag acacccctga tcgcacatta atgtcacaac agtccggcaa cgtaaagatc 9060acagtcaatg gccagacggt gcggtacaag tgtaattgcg gtggctcaaa tgaaggacta 9120acaactacag acaaagtgat taataactgc aaggttgatc aatgtcatgc cgcggtcacc 9180aatcacaaaa agtggcagta taactcccct ctggtcccgc gtaatgctga acttggggac 9240cgaaaaggaa aaattcacat cccgtttccg ctggcaaatg taacatgcag ggtgcctaaa 9300gcaaggaacc ccaccgtgac gtacgggaaa aaccaagtca tcatgctact gtatcctgac 9360cacccaacac tcctgtccta ccggaatatg ggagaagaac caaactatca agaagagtgg 9420gtgatgcata agaaggaagt cgtgctaacc gtgccgactg aagggctcga ggtcacgtgg 9480ggcaacaacg agccgtataa gtattggccg cagttatcta caaacggtac agcccatggc 9540cacccgcatg agataattct gtattattat gagctgtacc ccactatgac tgtagtagtt 9600gtgtcagtgg ccacgttcat actcctgtcg atggtgggta tggcagcggg gatgtgcatg 9660tgtgcacgac gcagatgcat cacaccgtat gaactgacac caggagctac cgtccctttc 9720ctgcttagcc taatatgctg catcagaaca gctaaagcgg ccacatacca agaggctgcg 9780atatacctgt ggaacgagca gcaacctttg ttttggctac aagcccttat tccgctggca 9840gccctgattg ttctatgcaa ctgtctgaga ctcttaccat gctgctgtaa aacgttggct 9900tttttagccg taatgagcgt cggtgcccac actgtgagcg cgtacgaaca cgtaacagtg 9960atcccgaaca cggtgggagt accgtataag actctagtca atagacctgg ctacagcccc 10020atggtattgg agatggaact actgtcagtc actttggagc caacactatc gcttgattac 10080atcacgtgcg agtacaaaac cgtcatcccg tctccgtacg tgaagtgctg cggtacagca 10140gagtgcaagg acaaaaacct acctgactac agctgtaagg tcttcaccgg cgtctaccca 10200tttatgtggg gcggcgccta ctgcttctgc gacgctgaaa acacgcagtt gagcgaagca 10260cacgtggaga agtccgaatc atgcaaaaca gaatttgcat cagcatacag ggctcatacc 10320gcatctgcat cagctaagct ccgcgtcctt taccaaggaa ataacatcac tgtaactgcc 10380tatgcaaacg gcgaccatgc cgtcacagtt aaggacgcca aattcattgt ggggccaatg 10440tcttcagcct ggacaccttt cgacaacaaa attgtggtgt acaaaggtga cgtctataac 10500atggactacc cgccctttgg cgcaggaaga ccaggacaat ttggcgatat ccaaagtcgc 10560acacctgaga gtaaagacgt ctatgctaat acacaactgg tactgcagag accggctgcg 10620ggtacggtac acgtgccata ctctcaggca ccatctggct ttaagtattg gctaaaagaa 10680cgcggggcgt cgctgcagca cacagcacca tttggctgcc aaatagcaac aaacccggta 10740agagcggtga actgcgccgt agggaacatg cccatctcca tcgacatacc ggaagcggcc 10800ttcactaggg tcgtcgacgc gccctcttta acggacatgt cgtgcgaggt accagcctgc 10860acccattcct cagactttgg gggcgtcgcc attattaaat atgcagccag caagaaaggc 10920aagtgtgcgg tgcattcgat gactaacgcc gtcactattc gggaagctga gatagaagtt 10980gaagggaatt ctcagctgca aatctctttc tcgacggcct tagccagcgc cgaattccgc 11040gtacaagtct gttctacaca agtacactgt gcagccgagt gccacccccc gaaggaccac 11100atagtcaact acccggcgtc acataccacc ctcggggtcc aggacatctc cgctacggcg 11160atgtcatggg tgcagaagat cacgggaggt gtgggactgg ttgttgctgt tgccgcactg 11220attctaatcg tggtgctatg cgtgtcgttc agcaggcact aacttgacaa ttaagtatga 11280aggtatatgt gtcccctaag agacacactg tacatagcaa ataatctata gatcaaaggg 11340ctacgcaacc cctgaatagt aacaaaatac aaaatcacta aaaattataa aaacagaaaa 11400atacataaat aggtatacgt gtcccctaag agacacattg tatgtaggtg ataagtatag 11460atcaaagggc cgaataaccc ctgaatagta acaaaatatg aaaatcaata aaaatcataa 11520aatagaaaaa ccataaacag aagtagttca aagggctata aaacccctga atagtaacaa 11580aacataaaat taataaaaat c 11601211601DNAChikungunya virus 2caaagcaaga gattaataac ccatcatgga tcctgtgtac gtggacatag acgctgacag 60cgcctttttg aaggccctgc aacgtgcgta ccccatgttt gaggtggaac caaggcaggt 120cacaccgaat gaccatgcta atgctagagc gttctcgcat ctagctataa aactaataga 180gcaggaaatt gaccccgact caaccatcct ggatatcggc agtgcgccag caaggaggat 240gatgtcggac aggaagtacc actgcgtctg cccgatgcgc agtgcggaag atcccgagag 300actcgccaat tatgcgagaa agctagcatc tgccgcagga aaagtcctgg acagaaacat 360ctctggaaag atcggggact tacaagcagt aatggccgtg ccagacacgg agacgccaac 420attctgctta cacacagacg tctcatgtag acagagagca gacgtcgcta tataccaaga 480cgtctatgct gtacacgcac ccacgtcgct ataccaccag gcgattaaag gggtccgagt 540ggcgtactgg gttgggttcg acacaacccc gttcatgtac aatgccatgg cgggtgccta 600cccctcatac tcgacaaact gggcagatga gcaggtactg aaggctaaga acataggatt 660atgttcaaca gacctgacgg aaggtagacg aggcaagttg tctattatga gagggaaaaa 720gctaaaaccg tgcgaccgtg tgctgttctc agtagggtca acgctctacc cggaaagccg 780caagctactt aagagctggc acctgccatc ggtgttccat ttaaagggca aactcagctt 840cacatgccgc tgtgatacag tggtttcgtg tgagggctac gtcgttaaga gaataacgat 900gagcccaggc ctttatggaa aaaccacagg gtatgcggta acccaccacg cagacggatt 960cctgatgtgc aagactaccg acacggttga cggcgaaaga gtgtcattct cggtgtgcac 1020atacgtgccg gcgaccattt gtgatcaaat gaccggcatc cttgctacag aagtcacgcc 1080ggaggatgca cagaagctgt tggtggggct gaaccagaga atagtggtta acggcagaac 1140gcaacggaat acgaacacca tgaaaaatta tctgcttccc gtggtcgccc aagccttcag 1200taagtgggca aaggagtgcc ggaaagacat ggaagatgaa aaactcctgg gggtcagaga 1260aagaacactg acctgctgct gtctatgggc attcaagaag cagaaaacac acacggtcta 1320caagaggcct gatacccagt caattcagaa ggttcaggcc gagtttgaca gctttgtggt 1380accgagtctg tggtcgtccg ggttgtcaat ccctttgagg actagaatca aatggttgtt 1440aagcaaggtg ccaaaaaccg acctgatccc atacagcgga gacgcccgag aagcccggga 1500cgcagaaaaa gaagcagagg aagaacgaga agcagaactg actcgcgaag ccctaccacc 1560tctacaggca gcacaggaag atgttcaggt cgaaatcgac gtggaacagc ttgaggacag 1620agcgggcgca ggaataatag agactccgag aggagctatc aaagttactg cccaaccaac 1680agaccacgtc gtgggagagt acctggtact ctccccgcag accgtactac gtagccagaa 1740gctcagtctg attcacgctt tggcggagca agtgaagacg tgcacgcaca acggacgagc 1800agggaggtat gcggtcgaag cgtacgacgg ccgagtccta gtgccctcag gctatgcaat 1860ctcgcctgaa gacttccaga gtctaagcga aagcgcaacg atggtgtata acgaaagaga 1920gttcgtaaac agaaagctac accatattgc gatgcacgga ccagccctga acaccgacga 1980agagtcgtat gagctggtga gggcagagag gacagaacac gagtacgtct acgacgtgga 2040tcagagaaga tgctgtaaga aggaagaagc cgcaggactg gtactggtgg gcgacttgac 2100taatccgccc taccacgaat tcgcatatga agggctaaaa atccgccctg cctgcccata 2160caaaattgca gtcataggag tcttcggagt accgggatct ggcaagtcag ctattatcaa 2220gaacctagtt accaggcagg acctggtgac tagcggaaag aaagaaaact gccaagaaat 2280caccaccgac gtgatgagac agagaggtct agagatatct gcacgtacgg ttgactcgct 2340gctcttgaat ggatgcaaca gaccagtcga cgtgttgtac gtagacgagg cgtttgcgtg 2400ccactctgga acgctacttg ctttgatcgc cttggtgaga ccaaggcaga aagttgtact 2460ttgtggtgac ccgaagcagt gcggcttctt caatatgatg cagatgaaag tcaactataa 2520tcacaacatc tgcacccaag tgtaccacaa aagtatctcc aggcggtgta cactgcctgt 2580gaccgccatt gtgtcatcgt tgcattacga aggcaaaatg cgcactacga atgagtacaa 2640caagccgatt gtagtggaca ctacaggctc aacaaaacct gaccctggag acctcgtgtt 2700aacgtgcttc agagggtggg ttaaacaact gcaaattgac tatcgtggat acgaggtcat 2760gacagcagcc gcatcccaag ggttaaccag aaaaggagtt tacgcagtta gacaaaaagt 2820taatgaaaac ccgctctatg catcaacgtc agagcacgtc aacgtactcc taacgcgtac 2880ggaaggtaaa ctggtatgga agacactttc cggcgacccg tggataaaga cgctgcagaa 2940cccaccgaaa ggaaacttca aagcaactat taaggagtgg gaggtggagc atgcatcaat 3000aatggcgggc atctgcagtc accaaatgac cttcgataca ttccaaaata aagccaacgt 3060ttgttgggct aagagcttgg tccctatcct cgaaacagcg gggataaaac taaatgatag 3120gcagtggtct cagataattc aagccttcaa agaagacaaa gcatactcac ctgaagtagc 3180cctgaatgaa atatgtacgc gcatgtatgg ggtggatcta gacagcgggc tattttctaa 3240accgttggtg tctgtgtatt acgcggataa ccactgggat aataggcctg gagggaaaat 3300gttcggattt aaccccgagg cagcatccat tctagaaaga aagtatccat tcacaaaagg 3360gaagtggaac

atcaacaagc agatctgcgt gactaccagg aggatagaag actttaaccc 3420taccaccaac atcataccgg ccaacaggag actaccacac tcattagtgg ccgaacaccg 3480cccagtaaaa ggggaaagaa tggaatggct ggttaacaag ataaacggcc accacgtgct 3540cctggtcagt ggctataacc ttgcactgcc tactaagaga gtcacttggg tagcgccgtt 3600aggtgtccgc ggagcggact acacatacaa cctagagttg ggtctgccag caacgcttgg 3660taggtatgac ctagtggtca taaacatcca cacacctttt cgcatacacc attaccaaca 3720gtgcgtcgac cacgcaatga aactgcaaat gctcgggggt gactcattga gactgctcaa 3780accgggcggc tctctattga tcagagcata tggttacgca gatagaacca gtgaacgagt 3840catctgcgta ttgggacgca agtttagatc gtctagagcg ttgaaaccac catgtgtcac 3900cagcaacact gagatgtttt tcctattcag caactttgac aatggcagaa ggaatttcac 3960aactcatgtc atgaacaatc aactgaatgc agccttcgta ggacaggtca cccgagcagg 4020atgtgcaccg tcgtaccggg taaaacgcat ggacatcgcg aagaacgatg aagagtgcgt 4080agtcaacgcc gctaaccctc gcgggttacc gggtgacggt gtttgcaagg cagtatacaa 4140aaaatggccg gagtccttta agaacagtgc aacaccagtg ggaaccgcaa aaacagttat 4200gtgcggtacg tatccagtaa tccacgctgt tggaccaaac ttctctaatt attcggagtc 4260tgaaggggac cgggaattgg cagctgccta tcgagaagtc gcaaaggaag taactaggct 4320gggagtaaat agtgtagcta tacctctcct ctccacaggt gtatactcag gagggaaaga 4380caggctgacc cagtcactga accacctctt tacagccatg gactcgacgg atgcagacgt 4440ggtcatctac tgccgcgaca aagaatggga gaagaaaata tctgaggcca tacagatgcg 4500gacccaagta gagctgctgg atgagcacat ctccatagac tgcgatattg ttcgcgtgca 4560ccctgacagc agcttggcag gcagaaaagg atacagcacc acggaaggcg cactgtactc 4620atatctagaa gggacccgtt ttcatcagac ggctgtggat atggcggaga tacatactat 4680gtggccaaag caaacagagg ccaatgagca agtctgccta tatgccctgg gggaaagtat 4740tgaatcgatc aggcagaaat gcccggtgga tgatgcagac gcatcatctc cccccaaaac 4800tgtcccgtgc ctttgccgtt acgctatgac tccagaacgc gtcacccggc ttcgcatgaa 4860ccacgtcaca agcataattg tgtgttcttc gtttcccctc ccaaagtaca aaatagaagg 4920agtgcaaaaa gtcaaatgct ctaaggtaat gctatttgac cacaacgtgc catcgcgcgt 4980aagtccaagg gaatatagat cttcccagga gtctgcacag gaggcgagta caatcacgtc 5040actgacgcat agtcaattcg acctaagcgt tgatggcgag atactgcccg tcccgccaga 5100cctggatgct gacgccccag ccctagaacc agcactagac gacggggcga cacacacgct 5160gccatccaca accggaaacc ttgcggccgt gtctgattgg gtaatgagca ccgtacctgt 5220cgcgccgccc agaagaaggc gagggagaaa cctgactgtg acatgtgacg agagagaagg 5280gaatataaca cccatggcta gcgtccgatt ctttagggca gagctgtgtc cggtcgtaca 5340agaaacagcg gagacgcgtg acacagcaat gtctcttcag gcaccaccga gtaccgccac 5400ggaaccgaat catccgccga tctccttcgg agcatcaagc gagacgttcc ccattacatt 5460tggggacttc aacgaaggag aaatcgaaag cttgtcttct gagctactaa ctttcggaga 5520cttcttacca ggagaagtgg atgacttgac agacagcgac tggtccacgt gctcagacac 5580ggacgacgag ttatgactag acagggcagg tgggtatata ttctcgtcgg acaccggtcc 5640aggtcattta caacagaagt cagtacgcca gtcagtgctg ccggtgaaca ccctggagga 5700agtccacgag gagaagtgtt acccacctaa gctggatgaa gcaaaggagc aactattact 5760taagaaactc caggagagtg catccatggc caacagaagc aggtatcagt cgcgcaaagt 5820agaaaacatg aaagcagcaa tcatccagag actaaagaga ggctgtagac tatacttaat 5880gtcagagacc ccaaaagtcc ctacttaccg gactacatat ccggcgcctg tgtactcgcc 5940tccgatcaac gtccgattgt ccaatcccga gtccgcagtg gcagcatgca atgagttctt 6000agctagaaac tatccaactg tctcatcata ccaaattacc gacgagtatg atgcatatct 6060agacatggtg gacgggtcgg agagttgcct ggaccgagcg acattcaatc cgtcaaaact 6120caggagctac ccgaaacagc acgcttacca cgcgccctcc atcagaagcg ctgtaccgtc 6180cccattccag aacacactac agaatgtact ggcagcagcc acgaaaagaa actgcaacgt 6240cacacagatg agggaattac ccactttgga ctcagcagta ttcaacgtgg agtgtttcaa 6300aaaattcgca tgcaaccaag aatactggga agaatttgct gccagcccta ttaggataac 6360aactgagaat ttagcaacct atgttactaa actaaaaggg ccaaaagcag cagcgctatt 6420cgcaaaaacc cataatctac tgccactaca ggaagtacca atggataggt tcacagtaga 6480tatgaaaagg gacgtgaagg tgactcctgg tacaaagcat acagaggaaa gacctaaggt 6540gcaggttata caggcggctg aacccttggc gacagcatac ctatgtggga ttcacagaga 6600gctggttagg aggctgaacg ccgtcctcct acccaatgta catacactat ttgacatgtc 6660tgccgaggat ttcgatgcca tcatagccgc acactttaag ccaggagaca ctgttttgga 6720aacggacata gcctcctttg ataagagcca agatgattca cttgcgctta ctgctttgat 6780gctgttagag gatttagggg tggatcactc cctgctggac ttgatagagg ctgctttcgg 6840agagatttcc agctgtcacc taccgacagg tacgcgcttc aagttcggcg ccatgatgaa 6900atcaggtatg ttcctaactc tgttcgtcaa cacattgtta aacatcacca tcgccagccg 6960agtgctggaa gatcgtctga caaaatccgc gtgtgcggcc ttcatcggcg acgacaacat 7020aatacatgga gtcgtctccg atgaattgat ggcagccaga tgtgccactt ggatgaacat 7080ggaagtgaag atcatagatg cagttgtatc cttgaaagcc ccttactttt gtggagggtt 7140tatactgcac gatactgtga caggaacagc ttgcagagtg gcagacccgc taaaaaggct 7200ttttaaactg ggcaaaccgc tagcggcagg tgacgaacaa gatgaagata gaagacgagc 7260gctggctgac gaagtgatca gatggcaacg aacagggcta attgatgagc tggagaaagc 7320ggtatactct aggtacgaag tgcagggtat atcagttgtg gtaatgtcca tggccacctt 7380tgcaagctcc agatccaact tcgagaagct cagaggaccc gtcataactt tgtacggcgg 7440tcctaaatag gtacgcacta cagctaccta ttttgcagaa gccgacagca agtatctaaa 7500cactaatcag ctacaatgga gttcatccca acccaaactt tttacaatag gaggtaccag 7560cctcgaccct ggactccgcg ccctactatc caagtcatca ggcccagacc gcgccctcag 7620aggcaagctg ggcaacttgc ccagctgatc tcagcagtta ataaactgac aatgcgcgcg 7680gtaccccaac agaagccacg caggaatcgg aagaataaga agcaaaagca aaaacaacag 7740gcgccacaaa acaacacaaa tcaaaagaag cagccaccta aaaagaaacc ggctcaaaag 7800aaaaagaagc cgggccgcag agagaggatg tgcatgaaaa tcgaaaatga ttgtattttc 7860gaagtcaagc acgaaggtaa ggtaacaggt tacgcgtgcc tggtggggga caaagtaatg 7920aaaccagcac acgtaaaggg gaccatcgat aacgcggacc tggccaaact ggcctttaag 7980cggtcatcta agtatgacct tgaatgcgcg cagatacccg tgcacatgaa gtccgacgct 8040tcgaagttca cccatgagaa accggagggg tactacaact ggcaccacgg agcagtacag 8100tactcaggag gccggttcac catccctaca ggtgctggca aaccagggga cagcggcaga 8160ccgatcttcg acaacaaggg acgcgtggtg gccatagtct taggaggagc taatgaagga 8220gcccgtacag ccctctcggt ggtgacctgg aataaagaca ttgtcactaa aatcaccccc 8280gagggggccg aagagtggag tcttgccatc ccagttatgt gcctgttggc aaacaccacg 8340ttcccctgct cccagccccc ttgcacgccc tgctgctacg aaaaggaacc ggaggaaacc 8400ctacgcatgc ttgaggacaa cgtcatgaga cctgggtact atcagctgct acaagcatcc 8460ttaacatgtt ctccccaccg ccagcgacgc agcaccaagg acaacttcaa tgtctataaa 8520gccacaagac catacttagc tcactgtccc gactgtggag aagggcactc gtgccatagt 8580cccgtagcac tagaacgcat cagaaatgaa gcgacagacg ggacgctgaa aatccaggtc 8640tccttgcaaa tcggaataaa gacggatgac agccacgatt ggaccaagct gcgttatatg 8700gacaaccaca tgccagcaga cgcagagagg gcggggctat ttgtaagaac atcagcaccg 8760tgtacgatta ctggaacaat gggacacttc atcctggccc gatgtccaaa aggggaaact 8820ctgacggtgg gattcactga cagtaggaag attagtcact catgtacgca cccatttcac 8880cacgaccctc ctgtgatagg tcgggaaaaa ttccattccc gaccgcggca cggtaaagag 8940ctaccttgca gcacgtacgt gcagagcacc gccgcaacta ccgaggagat agaggtacac 9000atgcccccag acacccctga tcgcacatta atgtcacaac agtccggcaa cgtaaagatc 9060acagtcaatg gccagacggt gcggtacaag tgtaattgcg gtggctcaaa tgaaggacta 9120acaactacag acaaagtgat taataactgc aaggttgatc aatgtcatgc cgcggtcacc 9180aatcacaaaa agtggcagta taactcccct ctggtcccgc gtaatgctga acttggggac 9240cgaaaaggaa aaattcacat cccgtttccg ctggcaaatg taacatgcag ggtgcctaaa 9300gcaaggaacc ccaccgtgac gtacgggaaa aaccaagtca tcatgctact gtatcctgac 9360cacccaacac tcctgtccta ccggaatatg ggagaagaac caaactatca agaagagtgg 9420gtgatgcata agaaggaagt cgtgctaacc gtgccgactg aagggctcga ggtcacgtgg 9480ggcaacaacg agccgtataa gtattggccg cagttatcta caaacggtac agcccatggc 9540cacccgcatg agataattct gtattattat gagctgtacc ccactatgac tgtagtagtt 9600gtgtcagtgg ccacgttcat actcctgtcg atggtgggta tggcagcggg gatgtgcatg 9660tgtgcacgac gcagatgcat cacaccgtat gaactgacac caggagctac cgtccctttc 9720ctgcttagcc taatatgctg catcagaaca gctaaagcgg ccacatacca agaggctgcg 9780atatacctgt ggaacgagca gcaacctttg ttttggctac aagcccttat tccgctggca 9840gccctgattg ttctatgcaa ctgtctgaga ctcttaccat gctgctgtaa aacgttggct 9900tttttagccg taatgagcgt cggtgcccac actgtgagcg cgtacgaaca cgtaacagtg 9960atcccgaaca cggtgggagt accgtataag actctagtca atagacctgg ctacagcccc 10020atggtattgg agatggaact actgtcagtc actttggagc caacactatc gcttgattac 10080atcacgtgcg agtacaaaac cgtcatcccg tctccgtacg tgaagtgctg cggtacagca 10140gagtgcaagg acaaaaacct acctgactac agctgtaagg tcttcaccgg cgtctaccca 10200tttatgtggg gcggcgccta ctgcttctgc gacgctgaaa acacgcagtt gagcgaagca 10260cacgtggaga agtccgaatc atgcaaaaca gaatttgcat cagcatacag ggctcatacc 10320gcatctgcat cagctaagct ccgcgtcctt taccaaggaa ataacatcac tgtaactgcc 10380tatgcaaacg gcgaccatgc cgtcacagtt aaggacgcca aattcattgt ggggccaatg 10440tcttcagcct ggacaccttt cgacaacaaa attgtggtgt acaaaggtga cgtctataac 10500atggactacc cgccctttgg cgcaggaaga ccaggacaat ttggcgatat ccaaagtcgc 10560acacctgaga gtaaagacgt ctatgctaat acacaactgg tactgcagag accggctgcg 10620ggtacggtac acgtgccata ctctcaggca ccatctggct ttaagtattg gctaaaagaa 10680cgcggggcgt cgctgcagca cacagcacca tttggctgcc aaatagcaac aaacccggta 10740agagcggtga actgcgccgt agggaacatg cccatctcca tcgacatacc ggaagcggcc 10800ttcactaggg tcgtcgacgc gccctcttta acggacatgt cgtgcgaggt accagcctgc 10860acccattcct cagactttgg gggcgtcgcc attattaaat atgcagccag caagaaaggc 10920aagtgtgcgg tgcattcgat gactaacgcc gtcactattc gggaagctga gatagaagtt 10980gaagggaatt ctcagctgca aatctctttc tcgacggcct tagccagcgc cgaattccgc 11040gtacaagtct gttctacaca agtacactgt gcagccgagt gccacccccc gaaggaccac 11100atagtcaact acccggcgtc acataccacc ctcggggtcc aggacatctc cgctacggcg 11160atgtcatggg tgcagaagat cacgggaggt gtgggactgg ttgttgctgt tgccgcactg 11220attctaatcg tggtgctatg cgtatcgttc agcaggcact aacttgacaa ttaagtatga 11280aggtatatgt gtcccctaag agacacactg tacatagcaa ataatctata gatcaaaggg 11340ctacgcaacc cctgaatagt aacaaaatac aaaatcacta aaaattataa aaacagaaaa 11400atacataaat aggtatacgt gtcccctaag agacacattg tatgtaggtg ataagtatag 11460atcaaagggc cgaataaccc ctgaatagta acaaaatatg aaaatcaata aaaatcataa 11520aatagaaaaa ccataaacag aagtagttca aagggctata aaacccctga atagtaacaa 11580aacataaaat taataaaaat c 11601311601DNAChikungunya virus 3caaagcaaga gattaataac ccatcatgga tcctgtgtac gtggacatag acgctgacag 60cgcctttttg aaggccctgc aacgtgcgta ccccatgttt gaggtggaac caaggcaggt 120cacaccgaat gaccatgcta atgctagagc gttctcgcat ctagctataa aactaataga 180gcaggaaatt gaccccgact caaccatcct ggatatcggc agtgcgccag caaggaggat 240gatgtcggac aggaagtacc actgcgtctg cccgatgcgc agtgcggaag atcccgagag 300actcgccaat tatgcgagaa agctagcatc tgccgcagga aaagtcctgg acagaaacat 360ctctggaaag atcggggact tacaagcagt aatggccgtg ccagacacgg agacgccaac 420attctgctta cacacagacg tctcatgtag acagagagca gacgtcgcta tataccaaga 480cgtctatgct gtacacgcac ccacgtcgct ataccaccag gcgattaaag gggtccgagt 540ggcgtactgg gttgggttcg acacaacccc gttcatgtac aatgccatgg cgggtgccta 600cccctcatac tcgacaaact gggcagatga gcaggtactg aaggctaaga acataggatt 660atgttcaaca gacctgacgg aaggtagacg aggcaagttg tctattatga gagggaaaaa 720gctaaaaccg tgcgaccgtg tgctgttctc agtagggtca acgctctacc cggaaagccg 780caagctactt aagagctggc acctgccatc ggtgttccat ttaaagggca aactcagctt 840cacatgccgc tgtgatacag tggtttcgtg tgagggctac gtcgttaaga gaataacgat 900gagcccaggc ctttatggaa aaaccacagg gtatgcggta acccaccacg cagacggatt 960cctgatgtgc aagactaccg acacggttga cggcgaaaga gtgtcattct cggtgtgcac 1020atacgtgccg gcgaccattt gtgatcaaat gaccggcatc cttgctacag aagtcacgcc 1080ggaggatgca cagaagctgt tggtggggct gaaccagaga atagtggtta acggcagaac 1140gcaacggaat acgaacacca tgaaaaatta tctgcttccc gtggtcgccc aagccttcag 1200taagtgggca aaggagtgcc ggaaagacat ggaagatgaa aaactcctgg gggtcagaga 1260aagaacactg acctgctgct gtctatgggc attcaagaag cagaaaacac acacggtcta 1320caagaggcct gatacccagt caattcagaa ggttcaggcc gagtttgaca gctttgtggt 1380accgagtctg tggtcgtccg ggttgtcaat ccctttgagg actagaatca aatggttgtt 1440aagcaaggtg ccaaaaaccg acctgatccc atacagcgga gacgcccgag aagcccggga 1500cgcagaaaaa gaagcagagg aagaacgaga agcagaactg actcgcgaag ccctaccacc 1560tctacaggca gcacaggaag atgttcaggt cgaaatcgac gtggaacagc ttgaggacag 1620agcgggcgca ggaataatag agactccgag aggagctatc aaagttactg cccaaccaac 1680agaccacgtc gtgggagagt acctggtact ctccccgcag accgtactac gtagccagaa 1740gctcagtctg attcacgctt tggcggagca agtgaagacg tgcacgcaca acggacgagc 1800agggaggtat gcggtcgaag cgtacgacgg ccgagtccta gtgccctcag gctatgcaat 1860ctcgcctgaa gacttccaga gtctaagcga aagcgcaacg atggtgtata acgaaagaga 1920gttcgtaaac agaaagctac accatattgc gatgcacgga ccagccctga acaccgacga 1980agagtcgtat gagctggtga gggcagagag gacagaacac gagtacgtct acgacgtgga 2040tcagagaaga tgctgtaaga aggaagaagc cgcaggactg gtactggtgg gcgacttgac 2100taatccgccc taccacgaat tcgcatatga agggctaaaa atccgccctg cctgcccata 2160caaaattgca gtcataggag tcttcggagt accgggatct ggcaagtcag ctattatcaa 2220gaacctagtt accaggcagg acctggtgac tagcggaaag aaagaaaact gccaagaaat 2280caccaccgac gtgatgagac agagaggtct agagatatct gcacgtacgg ttgactcgct 2340gctcttgaat ggatgcaaca gaccagtcga cgtgttgtac gtagacgagg cgtttgcgtg 2400ccactctgga acgctacttg ctttgatcgc cttggtgaga ccaaggcaga aagttgtact 2460ttgtggtgac ccgaagcagt gcggcttctt caatatgatg cagatgaaag tcaactataa 2520tcacaacatc tgcacccaag tgtaccacaa aagtatctcc aggcggtgta cactgcctgt 2580gaccgccatt gtgtcatcgt tgcattacga aggcaaaatg cgcactacga atgagtacaa 2640caagccgatt gtagtggaca ctacaggctc aacaaaacct gaccctggag acctcgtgtt 2700aacgtgcttc agagggtggg ttaaacaact gcaaattgac tatcgtggat acgaggtcat 2760gacagcagcc gcatcccaag ggttaaccag aaaaggagtt tacgcagtta gacaaaaagt 2820taatgaaaac ccgctctatg catcaacgtc agagcacgtc aacgtactcc taacgcgtac 2880ggaaggtaaa ctggtatgga agacactttc cggcgacccg tggataaaga cgctgcagaa 2940cccaccgaaa ggaaacttca aagcaactat taaggagtgg gaggtggagc atgcatcaat 3000aatggcgggc atctgcagtc accaaatgac cttcgataca ttccaaaata aagccaacgt 3060ttgttgggct aagagcttgg tccctatcct cgaaacagcg gggataaaac taaatgatag 3120gcagtggtct cagataattc aagccttcaa agaagacaaa gcatactcac ctgaagtagc 3180cctgaatgaa atatgtacgc gcatgtatgg ggtggatcta gacagcgggc tattttctaa 3240accgttggtg tctgtgtatt acgcggataa ccactgggat aataggcctg gagggaaaat 3300gttcggattt aaccccgagg cagcatccat tctagaaaga aagtatccat tcacaaaagg 3360gaagtggaac atcaacaagc agatctgcgt gactaccagg aggatagaag actttaaccc 3420taccaccaac atcataccgg ccaacaggag actaccacac tcattagtgg ccgaacaccg 3480cccagtaaaa ggggaaagaa tggaatggct ggttaacaag ataaacggcc accacgtgct 3540cctggtcagt ggctataacc ttgcactgcc tactaagaga gtcacttggg tagcgccgtt 3600aggtgtccgc ggagcggact acacatacaa cctagagttg ggtctgccag caacgcttgg 3660taggtatgac ctagtggtca taaacatcca cacacctttt cgcatacacc attaccaaca 3720gtgcgtcgac cacgcaatga aactgcaaat gctcgggggt gactcattga gactgctcaa 3780accgggcggc tctctattga tcagagcata tggttacgca gatagaacca gtgaacgagt 3840catctgcgta ttgggacgca agtttagatc gtctagagcg ttgaaaccac catgtgtcac 3900cagcaacact gagatgtttt tcctattcag caactttgac aatggcagaa ggaatttcac 3960aactcatgtc atgaacaatc aactgaatgc agccttcgta ggacaggtca cccgagcagg 4020atgtgcaccg tcgtaccggg taaaacgcat ggacatcgcg aagaacgatg aagagtgcgt 4080agtcaacgcc gctaaccctc gcgggttacc gggtgacggt gtttgcaagg cagtatacaa 4140aaaatggccg gagtccttta agaacagtgc aacaccagtg ggaaccgcaa aaacagttat 4200gtgcggtacg tatccagtaa tccacgctgt tggaccaaac ttctctaatt attcggagtc 4260tgaaggggac cgggaattgg cagctgccta tcgagaagtc gcaaaggaag taactaggct 4320gggagtaaat agtgtagcta tacctctcct ctccacaggt gtatactcag gagggaaaga 4380caggctgacc cagtcactga accacctctt tacagccatg gactcgacgg atgcagacgt 4440ggtcatctac tgccgcgaca aagaatggga gaagaaaata tctgaggcca tacagatgcg 4500gacccaagta gagctgctgg atgagcacat ctccatagac tgcgatattg ttcgcgtgca 4560ccctgacagc agcttggcag gcagaaaagg atacagcacc acggaaggcg cactgtactc 4620atatctagaa gggacccgtt ttcatcagac ggctgtggat atggcggaga tacatactat 4680gtggccaaag caaacagagg ccaatgagca agtctgccta tatgccctgg gggaaagtat 4740tgaatcgatc aggcagaaat gcccggtgga tgatgcagac gcatcatctc cccccaaaac 4800tgtcccgtgc ctttgccgtt acgctatgac tccagaacgc gtcacccggc ttcgcatgaa 4860ccacgtcaca agcataattg tgtgttcttc gtttcccctc ccaaagtaca aaatagaagg 4920agtgcaaaaa gtcaaatgct ctaaggtaat gctatttgac cacaacgtgc catcgcgcgt 4980aagtccaagg gaatatagat cttcccagga gtctgcacag gaggcgagta caatcacgtc 5040actgacgcat agtcaattcg acctaagcgt tgatggcgag atactgcccg tcccgtcaga 5100cctggatgct gacgccccag ccctagaacc agcactagac gacggggcga cacacacgct 5160gccatccaca accggaaacc ttgcggccgt gtctgattgg gtaatgagca ccgtacctgt 5220cgcgccgccc agaagaaggc gagggagaaa cctgactgtg acatgtgacg agagagaagg 5280gaatataaca cccatggcta gcgtccgatt ctttagggca gagctgtgtc cggtcgtaca 5340agaaacagcg gagacgcgtg acacagcaat gtctcttcag gcaccaccga gtaccgccac 5400ggaaccgaat catccgccga tctccttcgg agcatcaagc gagacgttcc ccattacatt 5460tggggacttc aacgaaggag aaatcgaaag cttgtcttct gagctactaa ctttcggaga 5520cttcttacca ggagaagtgg atgacttgac agacagcgac tggtccacgt gctcagacac 5580ggacgacgag ttatgactag acagggcagg tgggtatata ttctcgtcgg acaccggtcc 5640aggtcattta caacagaagt cagtacgcca gtcagtgctg ccggtgaaca ccctggagga 5700agtccacgag gagaagtgtt acccacctaa gctggatgaa gcaaaggagc aactattact 5760taagaaactc caggagagtg catccatggc caacagaagc aggtatcagt cgcgcaaagt 5820agaaaacatg aaagcagcaa tcatccagag actaaagaga ggctgtagac tatacttaat 5880gtcagagacc ccaaaagtcc ctacttaccg gactacatat ccggcgcctg tgtactcgcc 5940tccgatcaac gtccgattgt ccaatcccga gtccgcagtg gcagcatgca atgagttctt 6000agctagaaac tatccaactg tctcatcata ccaaattacc gacgagtatg atgcatatct 6060agacatggtg gacgggtcgg agagttgcct ggaccgagcg acattcaatc cgtcaaaact 6120caggagctac ccgaaacagc acgcttacca cgcgccctcc atcagaagcg ctgtaccgtc 6180cccattccag aacacactac agaatgtact ggcagcagcc acgaaaagaa actgcaacgt 6240cacacagatg agggaattac ccactttgga ctcagcagta ttcaacgtgg agtgtttcaa 6300aaaattcgca tgcaaccaag aatactggga agaatttgct gccagcccta ttaggataac 6360aactgagaat ttagcaacct atgttactaa actaaaaggg ccaaaagcag cagcgctatt 6420cgcaaaaacc cataatctac tgccactaca ggaagtacca atggataggt tcacagtaga 6480tatgaaaagg gacgtgaagg tgactcctgg tacaaagcat acagaggaaa gacctaaggt 6540gcaggttata caggcggctg aacccttggc gacagcatac ctatgtggga ttcacagaga 6600gctggttagg aggctgaacg ccgtcctcct acccaatgta catacactat ttgacatgtc 6660tgccgaggat ttcgatgcca tcatagccgc acactttaag ccaggagaca ctgttttgga 6720aacggacata gcctcctttg ataagagcca

agatgattca cttgcgctta ctgctttgat 6780gctgttagag gatttagggg tggatcactc cctgctggac ttgatagagg ctgctttcgg 6840agagatttcc agctgtcacc taccgacagg tacgcgcttc aagttcggcg ccatgatgaa 6900atcaggtatg ttcctaactc tgttcgtcaa cacattgtta aacatcacca tcgccagccg 6960agtgctggaa gatcgtctga caaaatccgc gtgcgcggcc ttcatcggcg acgacaacat 7020aatacatgga gtcgtctccg atgaattgat ggcagccaga tgtgccactt ggatgaacat 7080ggaagtgaag atcatagatg cagttgtatc cttgaaagcc ccttactttt gtggagggtt 7140tatactgcac gatactgtga caggaacagc ttgcagagtg gcagacccgc taaaaaggct 7200ttttaaactg ggcaaaccgc tagcggcagg tgacgaacaa gatgaagata gaagacgagc 7260gctggctgac gaagtgatca gatggcaacg aacagggcta attgatgagc tggagaaagc 7320ggtatactct aggtacgaag tgcagggtat atcagttgtg gtaatgtcca tggccacctt 7380tgcaagctcc agatccaact tcgagaagct cagaggaccc gtcataactt tgtacggcgg 7440tcctaaatag gtacgcacta cagctaccta ttttgcagaa gccgacagca agtatctaaa 7500cactaatcag ctacaatgga gttcatccca acccaaactt tttacaatag gaggtaccag 7560cctcgaccct ggactccgcg ccctactatc caagtcatca ggcccagacc gcgccctcag 7620aggcaagctg ggcaacttgc ccagctgatc tcagcagtta ataaactgac aatgcgcgcg 7680gtaccccaac agaagccacg caggaatcgg aagaataaga agcaaaagca aaaacaacag 7740gcgccacaaa acaacacaaa tcaaaagaag cagccaccta aaaagaaacc ggctcaaaag 7800aaaaagaagc cgggccgcag agagaggatg tgcatgaaaa tcgaaaatga ttgtattttc 7860gaagtcaagc acgaaggtaa ggtaacaggt tacgcgtgcc tggtggggga caaagtaatg 7920aaaccagcac acgtaaaggg gaccatcgat aacgcggacc tggccaaact ggcctttaag 7980cggtcatcta agtatgacct tgaatgcgcg cagatacccg tgcacatgaa gtccgacgct 8040tcgaagttca cccatgagaa accggagggg tactacaact ggcaccacgg agcagtacag 8100tactcaggag gccggttcac catccctaca ggtgctggca aaccagggga cagcggcaga 8160ccgatcttcg acaacaaggg acgcgtggtg gccatagtct taggaggagc taatgaagga 8220gcccgtacag ccctctcggt ggtgacctgg aataaagaca ttgtcactaa aatcaccccc 8280gagggggccg aagagtggag tcttgccatc ccagttatgt gcctgttggc aaacaccacg 8340ttcccctgct cccagccccc ttgcacgccc tgctgctacg aaaaggaacc ggaggaaacc 8400ctacgcatgc ttgaggacaa cgtcatgaga cctgggtact atcagctgct acaagcatcc 8460ttaacatgtt ctccccaccg ccagcgacgc agcaccaagg acaacttcaa tgtctataaa 8520gccacaagac catacttagc tcactgtccc gactgtggag aagggcactc gtgccatagt 8580cccgtagcac tagaacgcat cagaaatgaa gcgacagacg ggacgctgaa aatccaggtc 8640tccttgcaaa tcggaataaa gacggatgac agccacgatt ggaccaagct gcgttatatg 8700gacaaccaca tgccagcaga cgcagagagg gcggggctat ttgtaagaac atcagcaccg 8760tgtacgatta ctggaacaat gggacacttc atcctggccc gatgtccaaa aggggaaact 8820ctgacggtgg gattcactga cagtaggaag attagtcact catgtacgca cccatttcac 8880cacgaccctc ctgtgatagg tcgggaaaaa ttccattccc gaccgcagca cggtaaagag 8940ctaccttgca gcacgtacgt gcagagcacc gccgcaacta ccgaggagat agaggtacac 9000atgcccccag acacccctga tcgcacatta atgtcacaac agtccggcaa cgtaaagatc 9060acagtcaatg gccagacggt gcggtacaag tgtaattgcg gtggctcaaa tgaaggacta 9120acaactacag acaaagtgat taataactgc aaggttgatc aatgtcatgc cgcggtcacc 9180aatcacaaaa agtggcagta taactcccct ctggtcccgc gtaatgctga acttggggac 9240cgaaaaggaa aaattcacat cccgtttccg ctggcaaatg taacatgcag ggtgcctaaa 9300gcaaggaacc ccaccgtgac gtacgggaaa aaccaagtca tcatgctact gtatcctgac 9360cacccaacac tcctgtccta ccggaatatg ggagaagaac caaactatca agaagagtgg 9420gtgatgcata agaaggaagt cgtgctaacc gtgccgactg aagggctcga ggtcacgtgg 9480ggcaacaacg agccgtataa gtattggccg cagttatcta caaacggtac agcccatggc 9540cacccgcatg agataattct gtattattat gagctgtacc ccactatgac tgtagtagtt 9600gtgtcagtgg ccacgttcat actcctgtcg atggtgggta tggcagcggg gatgtgcatg 9660tgtgcacgac gcagatgcat cacaccgtat gaactgacac caggagctac cgtccctttc 9720ctgcttagcc taatatgctg catcagaaca gctaaagcgg ccacatacca agaggctgcg 9780atatacctgt ggaacgagca gcaacctttg ttttggctac aagcccttat tccgctggca 9840gccctgattg ttctatgcaa ctgtctgaga ctcttaccat gctgctgtaa aacgttggct 9900tttttagccg taatgagcgt cggtgcccac actgtgagcg cgtacgaaca cgtaacagtg 9960atcccgaaca cggtgggagt accgtataag actctagtca atagacctgg ctacagcccc 10020atggtattgg agatggaact actgtcagtc actttggagc caacactatc gcttgattac 10080atcacgtgcg agtacaaaac cgtcatcccg tctccgtacg tgaagtgctg cggtacagca 10140gagtgcaagg acaaaaacct acctgactac agctgtaagg tcttcaccgg cgtctaccca 10200tttatgtggg gcggcgccta ctgcttctgc gacgctgaaa acacgcagtt gagcgaagca 10260cacgtggaga agtccgaatc atgcaaaaca gaatttgcat cagcatacag ggctcatacc 10320gcatctgcat cagctaagct ccgcgtcctt taccaaggaa ataacatcac tgtaactgcc 10380tatgcaaacg gcgaccatgc cgtcacagtt aaggacgcca aattcattgt ggggccaatg 10440tcttcagcct ggacaccttt cgacaacaaa attgtggtgt acaaaggtga cgtctataac 10500atggactacc cgccctttgg cgcaggaaga ccaggacaat ttggcgatat ccaaagtcgc 10560acacctgaga gtaaagacgt ctatgctaat acacaactgg tactgcagag accggctgtg 10620ggtacggtac acgtgccata ctctcaggca ccatctggct ttaagtattg gctaaaagaa 10680cgcggggcgt cgctgcagca cacagcacca tttggctgcc aaatagcaac aaacccggta 10740agagcggtga actgcgccgt agggaacatg cccatctcca tcgacatacc ggaagcggcc 10800ttcactaggg tcgtcgacgc gccctcttta acggacatgt cgtgcgaggt accagcctgc 10860acccattcct cagactttgg gggcgtcgcc attattaaat atgcagccag caagaaaggc 10920aagtgtgcgg tgcattcgat gactaacgcc gtcactattc gggaagctga gatagaagtt 10980gaagggaatt ctcagctgca aatctctttc tcgacggcct tagccagcgc cgaattccgc 11040gtacaagtct gttctacaca agtacactgt gcagccgagt gccacccccc gaaggaccac 11100atagtcaact acccggcgtc acataccacc ctcggggtcc aggacatctc cgctacggcg 11160atgtcatggg tgcagaagat cacgggaggt gtgggactgg ttgttgctgt tgccgcactg 11220attctaatcg tggtgctatg cgtgtcgttc agcaggcact aacttgacaa ttaagtatga 11280aggtatatgt gtcccctaag agacacactg tacatagcaa ataatctata gatcaaaggg 11340ctacgcaacc cctgaatagt aacaaaatac aaaatcacta aaaattataa aaacagaaaa 11400atacataaat aggtatacgt gtcccctaag agacacattg tatgtaggtg ataagtatag 11460atcaaagggc cgaataaccc ctgaatagta acaaaatatg aaaatcaata aaaatcataa 11520aatagaaaaa ccataaacag aagtagttca aagggctata aaacccctga atagtaacaa 11580aacataaaat taataaaaat c 11601411598DNAChikungunya virus 4caaagcaaga gattaataac ccatcatgga tcctgtgtac gtggacatag acgctgacag 60cgcctttttg aaggccctgc aacgtgcgta ccccatgttt gaggtggaac caaggcaggt 120cacaccgaat gaccatgcta atgctagagc gttctcgcat ctagctataa aactaataga 180gcaggaaatt gaccccgact caaccatcct ggatatcggc agtgcgccag caaggaggat 240gatgtcggac aggaagtacc actgcgtctg cccgatgcgc agtgcggaag atcccgagag 300actcgccaat tatgcgagaa agctagcatc tgccgcagga aaagtcctgg acagaaacat 360ctctggaaag atcggggact tacaagcagt aatggccgtg ccagacacgg agacgccaac 420attctgctta cacacagacg tctcatgtag acagagagca gacgtcgcta tataccaaga 480cgtctatgct gtacacgcac ccacgtcgct ataccaccag gcgattaaag gggtccgagt 540ggcgtactgg gttgggttcg acacaacccc gttcatgtac aatgccatgg cgggtgccta 600cccctcatac tcgacaaact gggcagatga gcaggtactg aaggctaaga acataggatt 660atgttcaaca gacctgacgg aaggtagacg aggcaagttg tctattatga gagggaaaaa 720gctaaaaccg tgcgaccgtg tgctgttctc agtagggtca acgctctacc cggaaagccg 780caagctactt aagagctggc acctgccatc ggtgttccat ttaaagggca aactcagctt 840cacatgccgc tgtgatacag tggtttcgtg tgagggctac gtcgttaaga gaataacgat 900gagcccaggc ctttatggaa aaaccatagg gtatgcggta acccaccacg cagacggatt 960cctgatgtgc aagactaccg acacggttga cggcgaaaga gtgtcattct cggtgtgcac 1020atacgtgccg gcgaccattt gtgatcaaat gaccggcatc cttgctacag aagtcacgcc 1080ggaggatgca cagaagctgt tggtggggct gaaccagaga atagtggtta acggcagaac 1140gcaacggaat acgaacacca tgaaaaatta tctgcttccc gtggtcgccc aagccttcag 1200taagtgggca aaggagtgcc ggaaagacat ggaagatgaa aaactcctgg gggtcagaga 1260aagaacactg acctgctgct gtctatgggc attcaagaag cagaaaacac acacggtcta 1320caagaggcct gatacccagt caattcagaa ggttcaggcc gagtttgaca gctttgtggt 1380accgagtctg tggtcgtccg ggttgtcaat ccctttgagg actagaatca aatggttgtt 1440aagcaaggtg ccaaaaaccg acctgatccc atacagcgga gacgcccgag aagcccggga 1500cgcagaaaaa gaagcagagg aagaacgaga agcagaactg actcgcgaag ccctaccacc 1560tctacaggca gcacaggaag atgttcaggt cgaaatcgac gtggaacagc ttgaggacag 1620agcgggcgca ggaataatag agactccgag aggagctatc aaagttactg cccaaccaac 1680agaccacgtc gtgggagagt acctggtact ctccccgcag accgtactac gtagccagaa 1740gctcagtctg attcacgctt tggcggagca agtgaagacg tgcacgcaca acggacgagc 1800agggaggtat gcggtcgaag cgtacgacgg ccgagtccta gtgccctcag gctatgcaat 1860ctcgcctgaa gacttccaga gtctaagcga aagcgcaacg atggtgtata acgaaagaga 1920gttcgtaaac agaaagctac accatattgc gatgcacgga ccagccctga acaccgacga 1980agagtcgtat gagctggtga gggcagagag gacagaacac gagtacgtct acgacgtgga 2040tcagagaaga tgctgtaaga aggaagaagc cgcaggactg gtactggtgg gcgacttgac 2100taatccgccc taccacgaat tcgcatatga agggctaaaa atccgccctg cctgcccata 2160caaaattgca gtcataggag tcttcggagt accgggatct ggcaagtcag ctattatcaa 2220gaacctagtt accaggcagg acctggtgac tagcggaaag aaagaaaact gccaagaaat 2280caccaccgac gtgatgagac agagaggtct agagatatct gcacgtacgg ttgactcgct 2340gctcttgaat ggatgcaaca gaccagtcga cgtgttgtac gtagacgagg cgtttgcgtg 2400ccactctgga acgctacttg ctttgatcgc cttggtgaga ccaaggcaga aagttgtact 2460ttgtggtgac ccgaagcagt gcggcttctt caatatgatg cagatgaaag tcaactataa 2520tcacaacatc tgcacccaag tgtaccacaa aagtatctcc aggcggtgta cactgcctgt 2580gaccgccatt gtgtcatcgt tgcattacga aggcaaaatg cgcactacga atgagtacaa 2640caagccgatt gtagtggaca ctacaggctc aacaaaacct gaccctggag acctcgtgtt 2700aacgtgcttc agagggtggg ttaaacaact gcaaattgac tatcgtggat acgaggtcat 2760gacagcagcc gcatcccaag ggttaaccag aaaaggagtt tacgcagtta gacaaaaagt 2820taatgaaaac ccgctctatg catcaacgtc agagcacgtc aacgtactcc taacgcgtac 2880ggaaggtaaa ctggtatgga agacactttc cggcgacccg tggataaaga cgctgcagaa 2940cccaccgaaa ggaaacttca aagcaactat taaggagtgg gaggtggagc atgcatcaat 3000aatggcgggc atctgcagtc accaaatgac cttcgataca ttccaaaata aagccaacgt 3060ttgttgggct aagagcttgg tccctatcct cgaaacagcg gggataaaac taaatgatag 3120gcagtggtct cagataattc aagccttcaa agaagacaaa gcatactcac ctgaagtagc 3180cctgaatgaa atatgtacgc gcatgtatgg ggtggatcta gacagcgggc tattttctaa 3240accgttggtg tctgtgtatt acgcggataa ccactgggat aataggcctg gagggaaaat 3300gttcggattt aaccccgagg cagcatccat tctagaaaga aagtatccat tcacaaaagg 3360gaagtggaac atcaacaagc agatctgcgt gactaccagg aggatagaag actttaaccc 3420taccaccaac atcataccgg ccaacaggag actaccacac tcattagtgg ccgaacaccg 3480cccagtaaaa ggggaaagaa tggaatggct ggttaacaag ataaacggcc accacgtgct 3540cctggtcagt ggcaataacc ttgcactgcc tactaagaga gtcacttggg tagcgccgtt 3600aggtgtccgc ggagcggact acacatacaa cctagagttg ggtctgccag caacgcttgg 3660taggtatgac ctagtggtca taaacatcca cacacctttt cgcatacacc attaccaaca 3720gtgcgtcgac cacgcaatga aactgcaaat gctcgggggt gactcattga gactgctcaa 3780accgggcggc tctctattga tcagagcata tggttacgca gatagaacca gtgaacgagt 3840catctgcgta ttgggacgca agtttagatc gtctagagcg ttgaaaccac catgtgtcac 3900cagcaacact gagatgtttt tcctattcag caactttgac aatggcagaa ggaatttcac 3960aactcatgtc atgaacaatc aactgaatgc agccttcgta ggacaggtca cccgagcagg 4020atgtgcaccg tcgtaccggg taaaacgcat ggacatcgcg aagaacgatg aagagtgcgt 4080agtcaacgcc gctaaccctc gcgggttacc gggtgacggt gtttgcaagg cagtatacaa 4140aaaatggccg gagtccttta agaacagtgc aacaccagtg ggaaccgcaa aaacagttat 4200gtgcggtacg tatccagtaa tccacgctgt tggaccaaac ttctctaatt attcggagtc 4260tgaaggggac cgggaattgg cagctgccta tcgagaagtc gcaaaggaag taactaggct 4320gggagtaaat agtgtagcta tacctctcct ctccacaggt gtatactcag gagggaaaga 4380caggctgacc cagtcactga accacctctt tacagccatg gactcgacgg atgcagacgt 4440ggtcatctac tgccgcgaca aagaatggga gaagaaaata tctgaggcca tacagatgcg 4500gacccaagta gagctgctgg atgagcacat ctccatagac tgcgatattg ttcgcgtgca 4560ccctgacagc agcttggcag gcagaaaagg atacagcacc acggaaggcg cactgtactc 4620atatctagaa gggacccgtt ttcatcagac ggcagtggat atggcggaga tacatactat 4680gtggccaaag caaacagagg ccaatgagca agtctgccta tatgccctgg gggaaagtat 4740tgaatcgatc aggcagaaat gcccggtgga tgatgcagac gcatcatctc cccccaaaac 4800tgtcccgtgc ctttgccgtt acgctatgac tccagaacgc gtcacccggc ttcgcatgaa 4860ccacgtcaca agcataattg tgtgttcttc gtttcccctc ccaaagtaca aaatagaagg 4920agtgcaaaaa gtcaaatgct ctaaggtaat gctatttgac cacaacgtgc catcgcgcgt 4980aagtccaagg gaatatagat cttcccagga gtctgcacag gaggcgagta caatcacgtc 5040actgacgcat agtcaattcg acctaagcgt tgatggcgag atactgcccg tcccgtcaga 5100cctggatgct gacgccccag ccctagaacc agcactagac gacggggcga cacacacgct 5160gccatccaca accggaaacc ttgcggccgt gtctgattgg gtaatgagca ccgtacctgt 5220cgcgccgccc agaagaaggc gagggagaaa cctgactgtg acatgtgacg agagagaagg 5280gaatataaca cccatggcta gcgtccgatt ctttagggca gagctgtgtc cggtcgtaca 5340agaaacagcg gagacgcgtg acacagcaat gtctcttcag gcaccaccga gtaccgccac 5400accgaatcat ccgccgatct ccttcggagc atcaagcgag acgttcccca ttacatttgg 5460ggacttcaac gaaggagaaa tcgaaagctt gtcttctgag ctactaactt tcggagactt 5520cttaccagga gaagtggatg acttgacaga cagcgactgg tccacgtgct cagacacgga 5580cgacgagtta tgactagaca gggcaggtgg gtatatattc tcgtcggaca ccggtccagg 5640tcatttacaa cagaagtcag tacgccagtc agtgctgccg gtgaacaccc tggaggaagt 5700ccacgaggag aagtgttacc cacctaagct ggatgaagca aaggagcaac tattacttaa 5760gaaactccag gagagtgcat ccatggccaa cagaagcagg tatcagtcgc gcaaagtaga 5820aaacatgaaa gcagcaatca tccagagact aaagagaggc tgtagactat acttaatgtc 5880agagacccca aaagtcccta cttaccggac tacatatccg gcgcctgtgt actcgcctcc 5940gatcaacgtc cgattgtcca atcccgagtc cgcagtggca gcatgcaatg agttcttagc 6000tagaaactat ccaactgtct catcatacca aattaccgac gagtatgatg catatctaga 6060catggtggac gggtcggaga gttgcctgga ccgagcgaca ttcaatccgt caaaactcag 6120gagctacccg aaacagcacg cttaccacgc gccctccatc agaagcgctg taccgtcccc 6180attccagaac acactacaga atgtactggc agcagccacg aaaagaaact gcaacgtcac 6240acagatgagg gaattaccca ctttggactc agcagtattc aacgtggagt gtttcaaaaa 6300attcgcatgc aaccaagaat actgggaaga atttgctgcc agccctatta ggataacaac 6360tgagaattta gcaacctatg ttactaaact aaaagggcca aaagcagcag cgctattcgc 6420aaaaacccat aatctactgc cactacagga agtaccaatg gataggttca cagtagatat 6480gaaaagggac gtaaaggtga ctcctggtac aaagcataca gaggaaagac ctaaggtgca 6540ggttatacag gcggctgaac ccttggcgac agcataccta tgtgggattc acagagagct 6600ggttaggagg ctgaacgccg tcctcctacc caatgtacat acactatttg acatgtctgc 6660cgaggatttc gatgccatca tagccgcaca ctttaagcca ggagacactg ttttggaaac 6720ggacatagcc tcctttgata agagccaaga tgattcactt gcgcttactg ctttgatgct 6780gttagaggat ttaggggtgg atcactccct gctggacttg atagaggctg ctttcggaga 6840gatttccagc tgtcacctac cgacaggtac gcgcttcaag ttcggcgcca tgatgaaatc 6900aggtatgttc ctaactctgt tcgtcaacac attgttaaac atcaccatcg ccagccgagt 6960gctggaagat cgtctgacaa aatccgcgtg cgcggccttc atcggcgacg acaacataat 7020acatggagtc gtctccgatg aattgatggc agccagatgt gccacttgga tgaacatgga 7080agtgaagatc atagatgcag ttgtatcctt gaaagcccct tacttttgtg gagggtttat 7140actgcacgat actgtgacag gaacagcttg cagagtggca gacccgctaa aaaggctttt 7200taaactgggc aaaccgctag cggcaggtga cgaacaagat gaagatagaa gacgagcgct 7260ggctgacgaa gtgatcagat ggcaacgaac agggctaatt gatgagctgg agaaagcggt 7320atactctagg tacgaagtgc agggtatatc agttgtggta atgtccatgg ccacctttgc 7380aagctccaga tccaacttcg agaagctcag aggacccgtc ataactttgt acggcggtcc 7440taaataggta cgcactacag ctacctattt tgcagaagcc gacagcaagt atctaaacac 7500taatcagcta caatggagtt catcccaacc caaacttttt acaataggag gtaccagcct 7560cgaccctgga ctccgcgccc tactatccaa gtcatcaggc ccagaccgcg ccctcagagg 7620caagctgggc aacttgccca gctgatctca gcagttaata aactgacaat gcgcgcggta 7680ccccaacaga agccacgcag gaatcggaag aataagaagc aaaagcaaaa acaacaggcg 7740ccacaaaaca acacaaatca aaagaagcag ccacctaaaa agaaaccggc tcaaaagaaa 7800aagaagccgg gccgcagaga gaggatgtgc atgaaaatcg aaaatgattg tattttcgaa 7860gtcaagcacg aaggtaaggt aacaggttac gcgtgcctgg tgggggacaa agtaatgaaa 7920ccagcacacg taaaggggac catcgataac gcggacctgg ccaaactggc ctttaagcgg 7980tcatctaagt atgaccttga atgcgcgcag atacccgtgc acatgaagtc cgacgcttcg 8040aagttcaccc atgagaaacc ggaggggtac tacaactggc accacggagc agtacagtac 8100tcaggaggcc ggttcaccat ccctacaggt gctggcaaac caggggacag cggcagaccg 8160atcttcgaca acaagggacg cgtggtggcc atagtcttag gaggagctaa tgaaggagcc 8220cgtacagccc tctcggtggt gacctggaat aaagacattg tcactaaaat cacccccgag 8280ggggccgaag agtggagtct tgccatccca gttatgtgcc tgttggcaaa caccacgttc 8340ccctgctccc agcccccttg cacgccctgc tgctacgaaa aggaaccgga ggaaacccta 8400cgcatgcttg aggacaacgt catgagacct gggtactatc agctgctaca agcatcctta 8460acatgttctc cccaccgcca gcgacgcagc accaaggaca acttcaatgt ctataaagcc 8520acaagaccat acttagctca ctgtcccgac tgtggagaag ggcactcgtg ccatagtccc 8580gtagcactag aacgcatcag aaatgaagcg acagacggga cgctgaaaat ccaggtctcc 8640ttgcaaatcg gaataaagac ggatgacagc cacgattgga ccaagctgcg ttatatggac 8700aaccacatgc cagcagacgc agagagggcg gggctatttg taagaacatc agcaccgtgt 8760acgattactg gaacaatggg acacttcatc ctggcccgat gtccaaaagg ggaaactctg 8820acggtgggat tcactgacag taggaagatt agtcactcat gtacgcaccc atttcaccac 8880gaccctcctg tgataggtcg ggaaaaattc cattcccgac cgcagcacgg taaagagcta 8940ccttgcagca cgtacgtgca gagcaccgcc gcaactaccg aggagataga ggtacacatg 9000cccccagaca cccctgatcg cacattaatg tcacaacagt ccggcaacgt aaagatcaca 9060gtcaatggcc agacggtgcg gtacaagtgt aattgcggtg gctcaaatga aggactaaca 9120actacagaca aagtgattaa taactgcaag gttgatcaat gtcatgccgc ggtcaccaat 9180cacaaaaagt ggcagtataa ctcccctctg gtcccgcgta atgctgaact tggggaccga 9240aaaggaaaaa ttcacatccc gtttccgctg gcaaatgtaa catgcagggt gcctaaagca 9300aggaacccca ccgtgacgta cgggaaaaac caagtcatca tgctactgta tcctgaccac 9360ccaacactcc tgtcctaccg gaatatggga gaagaaccaa actatcaaga agagtgggtg 9420atgcataaga aggaagtcgt gctaaccgtg ccgactgaag ggctcgaggt cacgtggggc 9480aacaacgagc cgtataagta ttggccgcag ttatctacaa acggtacagc ccatggccac 9540ccgcatgaga taattctgta ttattatgag ctgtacccca ctatgactgt agtagttgtg 9600tcagtggcca cgttcatact cctgtcgatg gtgggtatgg cagcggggat gtgcatgtgt 9660gcacgacgca gatgcatcac accgtatgaa ctgacaccag gagctaccgt ccctttcctg 9720cttagcctaa tatgctgcat cagaacagct aaagcggcca cataccaaga ggctgcgata 9780tacctgtgga acgagcagca acctttgttt tggctacaag cccttattcc gctggcagcc 9840ctgattgttc tatgcaactg tctgagactc ttaccatgct gctgtaaaac gttggctttt 9900ttagccgtaa tgagcgtcgg tgcccacact gtgagcgcgt acgaacacgt aacagtgatc 9960ccgaacacgg tgggagtacc gtataagact ctagtcaata gacctggcta cagccccatg 10020gtattggaga tggaactact gtcagtcact ttggagccaa cactatcgct tgattacatc 10080acgtgcgagt acaaaaccgt catcccgtct ccgtacgtga agtgctgcgg tacagcagag

10140tgcaaggaca aaaacctacc tgactacagc tgtaaggtct tcaccggcgt ctacccattt 10200atgtggggcg gcgcctactg cttctgcgac gctgaaaaca cgcagttgag cgaagcacac 10260gtggagaagt ccgaatcatg caaaacagaa tttgcatcag catacagggc tcataccgca 10320tctgcatcag ctaagctccg cgtcctttac caaggaaata acatcactgt aactgcctat 10380gcaaacggcg accatgccgt cacagttaag gacgccaaat tcattgtggg gccaatgtct 10440tcagcctgga cacctttcga caacaaaatt gtggtgtaca aaggtgacgt ctataacatg 10500gactacccgc cctttggcgc aggaagacca ggacaatttg gcgatatcca aagtcgcaca 10560cctgagagta aagacgtcta tgctaataca caactggtac tgcagagacc ggctgtgggt 10620acggtacacg tgccatactc tcaggcacca tctggcttta agtattggct aaaagaacgc 10680ggggcgtcgc tgcagcacac agcaccattt ggctgccaaa tagcaacaaa cccggtaaga 10740gcggtgaact gcgccgtagg gaacatgccc atctccatcg acataccgga agcggccttc 10800actagggtcg tcgacgcgcc ctctttaacg gacatgtcgt gcgaggtacc agcctgcacc 10860cattcctcag actttggggg cgtcgccatt attaaatatg cagccagcaa gaaaggcaag 10920tgtgcggtgc attcgatgac taacgccgtc actattcggg aagctgagat agaagttgaa 10980gggaattctc agctgcaaat ctctttctcg acggccttag ccagcgccga attccgcgta 11040caagtctgtt ctacacaagt acactgtgca gccgagtgcc accccccgaa ggaccacata 11100gtcaactacc cggcgtcaca taccaccctc ggggtccagg acatctccgc tacggcgatg 11160tcatgggtgc agaagatcac gggaggtgtg ggactggttg ttgctgttgc cgcactgatt 11220ctaatcgtgg tgctatgcgt gtcgttcagc aggcactaac ttgacaatta agtatgaagg 11280tatatgtgtc ccctaagaga cacactgtac atagcaaata atctatagat caaagggcta 11340cgcaacccct gaatagtaac aaaatacaaa atcactaaaa attataaaaa cagaaaaata 11400cataaatagg tatacgtgtc ccctaagaga cacattgtat gtaggtgata agtatagatc 11460aaagggccga ataacccctg aatagtaaca aaatatgaaa atcaataaaa atcataaaat 11520agaaaaacca taaacagaag tagttcaaag ggctataaaa cccctgaata gtaacaaaac 11580ataaaattaa taaaaatc 11598511601DNAChikungunya virus 5caaagcaaga gattaataac ccatcatgga tcctgtgtac gtggacatag acgctgacag 60cgcctttttg aaggccctgc aacgtgcgta ccccatgttt gaggtggaac caaggcaggt 120cacaccgaat gaccatgcta atgctagagc gttctcgcat ctagctataa aactaataga 180gcaggaaatt gaccccgact caaccatcct ggatatcggc agtgcgccag caaggaggat 240gatgtcggac aggaagtacc actgcgtctg cccgatgcgc agtgcggaag atcccgagag 300actcgccaat tatgcgagaa agctagcatc tgccgcagga aaagtcctgg acagaaacat 360ctctggaaag atcggggact tacaagcagt aatggccgtg ccagacacgg agacgccaac 420attctgctta cacacagacg tctcatgtag acagagagca gacgtcgcta tataccaaga 480cgtctatgct gtacacgcac ccacgtcgct ataccaccag gcgattaaag gggtccgagt 540ggcgtactgg gttgggttcg acacaacccc gttcatgtac aatgccatgg cgggtgccta 600cccctcatac tcgacaaact gggcagatga gcaggtactg aaggctaaga acataggatt 660atgttcaaca gacctgacgg aaggtagacg aggcaagttg tctattatga gagggaaaaa 720gctaaaaccg tgcgaccgtg tgctgttctc agtagggtca acgctctacc cggaaagccg 780caagctactt aagagctggc acctgccatc ggtgttccat ttaaagggca aactcagctt 840cacatgccgc tgtgatacag tggtttcgtg tgagggctac gtcgttaaga gaataacgat 900gagcccaggc ctttatggaa aaaccacagg gtatgcggta acccaccacg cagacggatt 960cctgatgtgc aagactaccg acacggttga cggcgaaaga gtgtcattct cggtgtgcac 1020atacgtgccg gcgaccattt gtgatcaaat gaccggcatc cttgctacag aagtcacgcc 1080ggaggatgca cagaagctgt tggtggggct gaaccagaga atagtggtta acggcagaac 1140gcaacggaat acgaacacca tgaaaaatta tctgcttccc gtggtcgccc aagccttcag 1200taagtgggca aaggagtgcc ggaaagacat ggaagatgaa aaactcctgg gggtcagaga 1260aagaacactg acctgctgct gtctatgggc attcaagaag cagaaaacac acacggtcta 1320caagagacct gatacccagt caattcagaa ggttcaggcc gagtttgaca gctttgtggt 1380accgagtctg tggtcgtccg ggttgtcaat ccctttgagg actagaatca aatggttgtt 1440aagcaaggtg ccaaaaaccg acctgatccc atacagcgga gacgcccgag aagcccggga 1500cgcagaaaaa gaagcagagg aagaacgaga agcagaactg actcgcgaag ccctaccacc 1560tctacaggca gcacaggaag atgttcaggt cgaaatcgac gtggaacagc ttgaggacag 1620agcgggcgca ggaataatag agactccgag aggagctatc aaagttactg cccaaccaac 1680agaccacgtc gtgggagagt acctggtact ctccccgcag accgtactac gtagccagaa 1740gctcagtctg attcacgctt tggcggagca agtgaagacg tgcacgcaca acggacgagc 1800agggaggtat gcggtcgaag cgtacgacgg ccgagtccta gtgccctcag gctatgcaat 1860ctcgcctgaa gacttccaga gtctaagcga aagcgcaacg atggtgtata acgaaagaga 1920gttcgtaaac agaaagctac accatattgc gatgcacgga ccagccctga acaccgacga 1980agagtcgtat gagctggtga gggcagagag gacagaacac gagtacgtct acgacgtgga 2040tcagagaaga tgctgtaaga aggaagaagc cgcaggactg gtactggtgg gcgacttgac 2100taatccgccc taccacgaat tcgcatatga agggctaaaa atccgccctg cctgcccata 2160caaaattgca gtcataggag tcttcggagt accgggatct ggcaagtcag ctattatcaa 2220gaacctagtt accaggcagg acctggtgac tagcggaaag aaagaaaact gccaagaaat 2280caccaccgac gtgatgagac agagaggtct agagatatct gcacgtacgg ttgactcgct 2340gctcttgaat ggatgcaaca gaccagtcga cgtgttgtac gtagacgagg cgtttgcgtg 2400ccactctgga acgctacttg ctttgatcgc cttggtgaga ccaaggcaga aagttgtact 2460ttgtggtgac ccgaagcagt gcggcttctt caatatgatg cagatgaaag tcaactataa 2520tcacaacatc tgcacccaag tgtaccacaa aagtatctcc aggcggtgta cactgcctgt 2580gaccgccatt gtgtcatcgt tgcattacga aggcaaaatg cgcactacga atgagtacaa 2640caagccgatt gtagtggaca ctacaggctc aacaaaacct gaccctggag acctcgtgtt 2700aacgtgcttc agagggtggg ttaaacaact gcaaattgac tatcgtggat acgaggtcat 2760gacagcagcc gcatcccaag ggttaaccag aaaaggagtt tacgcagtta gacaaaaagt 2820taatgaaaac ccgctctatg catcaacgtc agagcacgtc aacgtactcc taacgcgtac 2880ggaaggtaaa ctggtatgga agacactttc cggcgacccg tggataaaga cgctgcagaa 2940cccaccgaaa ggaaacttca aagcaactat taaggagtgg gaggtggagc atgcatcaat 3000aatggcgggc atctgcagtc accaaatgac cttcgataca ttccaaaata aagccaacgt 3060ttgttgggct aagagcttgg tccctatcct cgaaacagcg gggataaaac taaatgatag 3120gcagtggtct cagataattc aagccttcaa agaagacaaa gcatactcac ctgaagtagc 3180cctgaatgaa atatgtacgc gcatgtatgg ggtggatcta gacagcgggc tattttctaa 3240accgttggtg tctgtgtatt acgcggataa ccactgggat aataggcctg gagggaaaat 3300gttcggattt aaccccgagg cagcatccat tctagaaaga aagtatccat tcacaaaagg 3360gaagtggaac atcaacaagc agatctgcgt gactaccagg aggatagaag actttaaccc 3420taccaccaac atcataccgg ccaacaggag actaccacac tcattagtgg ccgaacaccg 3480cccagtaaaa ggggaaagaa tggaatggct ggttaacaag ataaacggcc accacgtgct 3540cctggtcagt ggctataacc ttgcactgcc tactaagaga gtcacttggg tagcgccgtt 3600aggtgtccgc ggagcggact acacatacaa cctagagttg ggtctgccag caacgcttgg 3660taggtatgac ctagtggtca taaacatcca cacacctttt cgcatacacc attaccaaca 3720gtgcgtcgac cacgcaatga aactgcaaat gctcgggggt gactcattga gactgctcaa 3780accgggcggc tctctattga tcagagcata tggttacgca gatagaacca gtgaacgagt 3840catctgcgta ttgggacgca agtttagatc gtctagagcg ttgaaaccac catgtgtcac 3900cagcaacact gagatgtttt tcctattcag caactttgac aatggcagaa ggaatttcac 3960aactcatgtc atgaacaatc aactgaatgc agccttcgta ggacaggtca cccgagcagg 4020atgtgcaccg tcgtaccggg taaaacgcat ggacatcgcg aagaacgatg aagagtgcgt 4080agtcaacgcc gctaaccctc gcgggttacc gggtgacggt gtttgcaagg cagtatacaa 4140aaaatggccg gagtccttta agaacagtgc aacaccagtg ggaaccgcaa aaacagttat 4200gtgcggtacg tatccagtaa tccacgctgt tggaccaaac ttctctaatt attcggagtc 4260tgaaggggac cgggaattgg cagctgccta tcgagaagtc gcaaaggaag taactaggct 4320gggagtaaat agtgtagcta tacctctcct ctccacaggt gtatactcag gagggaaaga 4380caggctgacc cagtcactga accacctctt tacagccatg gactcgacgg atgcagacgt 4440ggtcatctac tgccgcgaca aagaatggga gaagaaaata tctgaggcca tacagatgcg 4500gacccaagta gagctgctgg atgagcacat ctccatagac tgcgatattg ttcgcgtgca 4560ccctgacagc agcttggcag gcagaaaagg atacagcacc acggaaggcg cactgtactc 4620atatctagaa gggacccgtt ttcatcagac ggctgtggat atggcggaga tacatactat 4680gtggccaaag caaacagagg ccaatgagca agtctgccta tatgccctgg gggaaagtat 4740tgaatcgatc aggcagaaat gcccggtgga tgatgcagac gcatcatctc cccccaaaac 4800tgtcccgtgc ctttgccgtt acgctatgac tccagaacgc gtcacccggc ttcgcatgaa 4860ccacgtcaca agcataattg tgtgttcttc gtttcccctc ccaaagtaca aaatagaagg 4920agtgcaaaaa gtcaaatgct ctaaggtaat gctatttgac cacaacgtgc catcgcgcgt 4980aagtccaagg gaatatagat cttcccagga gtctgcacag gaggcgagta caatcacgtc 5040actgacgcat agtcaattcg acctaagcgt tgatggcgag atactgcccg tcccgtcaga 5100cctggatgct gacgccccag ccctagaacc agcactagac gacggggcga cacacacgct 5160gccatccaca accggaaacc ttgcggccgt gtctgattgg gtaatgagca ccgtacctgt 5220cgcgccgccc agaagaaggc gagggagaaa cctgactgtg acatgtgacg agagagaagg 5280gaatataaca cccatggcta gcgtccgatt ctttagggca gagctgtgtc cggtcgtaca 5340agaaacagcg gagacgcgtg acacagcaat gtctcttcag gcaccaccga gtaccgccac 5400ggaaccgaat catccgccga tctccttcgg agcatcaagc gagacgttcc ccattacatt 5460tggggacttc aacgaaggag aaatcgaaag cttgtcttct gagctactaa ctttcggaga 5520cttcttacca ggagaagtgg atgacttgac agacagcgac tggtccacgt gctcagacac 5580ggacgacgag ttatgactag acagggcagg tgggtatata ttctcgtcgg acaccggtcc 5640aggtcattta caacagaagt cagtacgcca gtcagtgctg ccggtgaaca ccctggagga 5700agtccacgag gagaagtgtt acccacctaa gctggatgaa gcaaaggagc aactattact 5760taagaaactc caggagagtg catccatggc caacagaagc aggtatcagt cgcgcaaagt 5820agaaaacatg aaagcagcaa tcatccagag actaaagaga ggctgtagac tatacttaat 5880gtcagagacc ccaaaagtcc ctacttaccg gactacatat ccggcgcctg tgtactcgcc 5940tccgatcaac gtccgattgt ccaatcccga gtccgcagtg gcagcatgca atgagttctt 6000agctagaaac tatccaactg tctcatcata ccaaattacc gacgagtatg atgcatatct 6060agacatggtg gacgggtcgg agagttgcct ggaccgagcg acattcaatc cgtcaaaact 6120caggagctac ccgaaacagc acgcttacca cgcgccctcc atcagaagcg ctgtaccgtc 6180cccattccag aacacactac agaatgtact ggcagcagcc acgaaaagaa actgcaacgt 6240cacacagatg agggaattac ccactttgga ctcagcagta ttcaacgtgg agtgtttcaa 6300aaaattcgca tgcaaccaag aatactggga agaatttgct gccagcccta ttaggataac 6360aactgagaat ttagcaacct atgttactaa actaaaaggg ccaaaagcag cagcgctatt 6420cgcaaaaacc cataatctac tgccactaca ggaagtacca atggataggt tcacagtaga 6480tatgaaaagg gacgtaaagg tgactcctgg tacaaagcat acagaggaaa gacctaaggt 6540gcaggttata caggcggctg aacccttggc gacagcatac ctatgtggga ttcacagaga 6600gctggttagg aggctgaacg ccgtcctcct acccaatgta catacactat ttgacatgtc 6660tgccgaggat ttcgatgcca tcatagccgc acactttaag ccaggagaca ctgttttgga 6720aacggacata gcctcctttg ataagagcca agatgattca cttgcgctta ctgctttgat 6780gctgttagag gatttagggg tggatcactc cctgctggac ttgatagagg ctgctttcgg 6840agagatttcc agctgtcacc taccgacagg tacgcgcttc aagttcggcg ccatgatgaa 6900atcaggtatg ttcctaactc tgttcgtcaa cacattgtta aacatcacca tcgccagccg 6960agtgctggaa gatcgtctga caaaatccgc gtgcgcggcc ttcatcggcg acgacaacat 7020aatacatgga gtcgtctccg atgaattgat ggcagccaga tgtgccactt ggatgaacat 7080ggaagtgaag atcatagatg cagttgtatc cttgaaagcc ccttactttt gtggagggtt 7140tatactgcac gatactgtga caggaacagc ttgcagagtg gcagacccgc taaaaaggct 7200ttttaaactg ggcaaaccgc tagcggcagg tgacgaacaa gatgaagata gaagacgagc 7260gctggctgac gaagtgatca gatggcaacg aacagggcta attgatgagc tggagaaagc 7320ggtatactct aggtacgaag tgcagggtat atcagttgtg gtaatgtcca tggccacctt 7380tgcaagctcc agatccaact tcgagaagct cagaggaccc gtcataactt tgtacggcgg 7440tcctaaatag gtacgcacta cagctaccta ttttgcagaa gccgacagca agtatctaaa 7500cactaatcag ctacaatgga gttcatccca acccaaactt tttacaatag gaggtaccag 7560cctcgaccct ggactccgcg ccctactatc caagtcatca ggcccagacc gcgccctcag 7620aggcaagctg ggcaacttgc ccagctgatc tcagcagtta ataaactgac aatgcgcgcg 7680gtaccccaac agaagccacg caggaatcgg aagaataaga agcaaaagca aaaacaacag 7740gcgccacaaa acaacacaaa tcaaaagaag cagccaccta aaaagaaacc ggctcaaaag 7800aaaaagaagc cgggccgcag agagaggatg tgcatgaaaa tcgaaaatga ttgtattttc 7860gaagtcaagc acgaaggtaa ggtaacaggt tacgcgtgcc tggtggggga caaagtaatg 7920aaaccagcac acgtaaaggg gaccatcgat aacgcggacc tggccaaact ggcctttaag 7980cggtcatcta agtatgacct tgaatgcgcg cagatacccg tgcacatgaa gtccgacgct 8040tcgaagttca cccatgagaa accggagggg tactacaact ggcaccacgg agcagtacag 8100tactcaggag gccggttcac catccctaca ggtgctggca aaccagggga cagcggcaga 8160ccgatcttcg acaacaaggg acgcgtggtg gccatagtct taggaggagc taatgaagga 8220gcccgtacag ccctctcggt ggtgacctgg aataaagaca ttgtcactaa aatcaccccc 8280gagggggccg aagagtggag tcttgccatc ccagttatgt gcctgttggc aaacaccacg 8340ttcccctgct cccagccccc ttgcacgccc tgctgctacg aaaaggaacc ggaggaaacc 8400ctacgcatgc ttgaggacaa cgtcatgaga cctgggtact atcagctgct acaagcatcc 8460ttaacatgtt ctccccaccg ccagcgacgc agcaccaagg acaacttcaa tgtctataaa 8520gccacaagac catacttagc tcactgtccc gactgtggag aagggcactc gtgccatagt 8580cccgtagcac tagaacgcat cagaaatgaa gcgacagacg ggacgctgaa aatccaggtc 8640tccttgcaaa tcggaataaa gacggatgac agccacgatt ggaccaagct gcgttatatg 8700gacaaccaca tgccagcaga cgcagagagg gcggggctat ttgtaagaac atcagcaccg 8760tgtacgatta ctggaacaat gggacacttc atcctggccc gatgtccaaa aggggaaact 8820ctgacggtgg gattcactga cagtaggaag attagtcact catgtacgca cccatttcac 8880cacgaccctc ctgtgatagg tcgggaaaaa ttccattccc gaccgcagca cggtaaagag 8940ctaccttgca gcacgtacgt gcagagcacc gccgcaacta ccgaggagat agaggtacac 9000atgcccccag acacccctga tcgcacatta atgtcacaac agtccggcaa cgtaaagatc 9060acagtcaatg gccagacggt gcggtacaag tgtaattgcg gtggctcaaa tgaaggacta 9120acaactacag acaaagtgat taataactgc aaggttgatc aatgtcatgc cgcggtcacc 9180aatcacaaaa agtggcagta taactcccct ctggtcccgc gtaatgctga acttggggac 9240cgaaaaggaa aaattcacat cccgtttccg ctggcaaatg taacatgcag ggtgcctaaa 9300gcaaggaacc ccaccgtgac gtacgggaaa aaccaagtca tcatgctact gtatcctgac 9360cacccaacac tcctgtccta ccggaatatg ggagaagaac caaactatca agaagagtgg 9420gtgatgcata agaaggaagt cgtgctaacc gtgccgactg aagggctcga ggtcacgtgg 9480ggcaacaacg agccgtataa gtattggccg cagttatcta caaacggtac agcccatggc 9540cacccgcacg agataattct gtattattat gagctgtacc ccactatgac tgtagtagtt 9600gtgtcagtgg ccacgttcat actcctgtcg atggtgggta tggcagcggg gatgtgcatg 9660tgtgcacgac gcagatgcat cacaccgtat gaactgacac caggagctac cgtccctttc 9720ctgcttagcc taatatgctg catcagaaca gctaaagcgg ccacatacca agaggctgcg 9780atatacctgt ggaacgagca gcaacctttg ttttggctac aagcccttat tccgctggca 9840gccctgattg ttctatgcaa ctgtctgaga ctcttaccat gctgctgtaa aacgttggct 9900tttttagccg taatgagcgt cggtgcccac actgtgagcg cgtacgaaca cgtaacagtg 9960atcccgaaca cggtgggagt accgtataag actctagtca atagacctgg ctacagcccc 10020atggtattgg agatggaact actgtcagtc actttggagc caacactatc gcttgattac 10080atcacgtgcg agtacaaaac cgtcatcccg tctccgtacg tgaagtgctg cggtacagca 10140gagtgcaagg acaaaaacct acctgactac agctgtaagg tcttcaccgg cgtctaccca 10200tttatgtggg gcggcgccta ctgcttctgc gacgctgaaa acacgcagtt gagcgaagca 10260cacgtggaga agtccgaatc atgcaaaaca gaatttgcat cagcatacag ggctcatacc 10320gcatctgcat cagctaagct ccgcgtcctt taccaaggaa ataacatcac tgtaactgcc 10380tatgcaaacg gcgaccatgc cgtcacagtt aaggacgcca aattcattgt ggggccaatg 10440tcttcagcct ggacaccttt cgacaacaaa attgtggtgt acaaaggtga cgtctataac 10500atggactacc cgccctttgg cgcaggaaga ccaggacaat ttggcgatat ccaaagtcgc 10560acacctgaga gtaaagacgt ctatgctaat acacaactgg tactgcagag accggctgtg 10620ggtacggtac acgtgccata ctctcaggca ccatctggct ttaagtattg gctaaaagaa 10680cgcggggcgt cgctgcagca cacagcacca tttggctgcc aaatagcaac aaacccggta 10740agagcggtga actgcgccgt agggaacatg cccatctcca tcgacatacc ggaagcggcc 10800ttcactaggg tcgtcgacgc gccctcttta acggacatgt cgtgcgaggt accagcctgc 10860acccattcct cagactttgg gggcgtcgcc attattaaat atgcagccag caagaaaggc 10920aagtgtgcgg tgcattcgat gactaacgcc gtcactattc gggaagctga gatagaagtt 10980gaagggaatt ctcagctgca aatctctttc tcgacggcct tagccagcgc cgaattccgc 11040gtacaagtct gttctacaca agtacactgt gcagccgagt gccacccccc gaaggaccac 11100atagtcaact acccggcgtc acataccacc ctcggggtcc aggacatctc cgctacggcg 11160atgtcatggg tgcagaagat cacgggaggt gtgggactgg ttgttgctgt tgccgcactg 11220attctaatcg tggtgctatg cgtgtcgttc agcaggcact aacttgacaa ttaagtatga 11280aggtatatgt gtcccctaag agacacactg tacatagcaa ataatctata gatcaaaggg 11340ctacgcaacc cctgaatagt aacaaaatat aaaatcacta aaaattataa aaacagaaaa 11400atacataaat aggtatacgt gtcccctaag agacacattg tatgtaggtg ataagtatag 11460atcaaagggc cgaataaccc ctgaatagta acaaaatatg aaaatcaata aaaatcataa 11520aatagaaaaa ccataaacag aagtagttca aagggctata aaacccctga atagtaacaa 11580aacataaaat taataaaaat c 11601611237DNAChikungunya virus 6cagtttctta ctgctctact ctgcaaagca agagattaat aacccatcat ggatcctgtg 60tacgtggaca tagacgctga cagcgccttt ttgaaggccc tgcaacgtgc gtaccccatg 120tttgaggtgg aaccaaggca ggtcacaccg aatgaccatg ctaatgctag agcgttctcg 180catctagcta taaaactaat agagcaggaa attgaccccg actcaaccat cctggatatc 240ggcagtgcgc cagcaaggag gatgatgtcg gacaggaagt accactgcgt ctgcccgatg 300cgcagtgcgg aagatcccga gagactcgcc aattatgcga gaaagctagc atctgccgca 360ggaaaagtcc tggacagaaa catctctgga aagatcgggg acttacaagc agtaatggcc 420gtgccagaca cggagacgcc aacattctgc ttacacacag acgtctcatg tagacagaga 480gcagacgtcg ctatatacca agacgtctat gctgtacacg cacccacgtc gctataccac 540caggcgatta aaggggtccg agtggcgtac tgggttgggt tcgacacaac cccgttcatg 600tacaatgcca tggcgggtgc ctacccctca tactcgacaa actgggcaga tgagcaggta 660ctgaaggcta agaacatagg attatgttca acagacctga cggaaggtag acgaggcaag 720ttgtctatta tgagagggaa aaagctaaaa ccgtgcgacc gtgtgctgtt ctcagtaggg 780tcaacgctct acccggaaag ccgcaagcta cttaagagct ggcacctgcc atcggtgttc 840catttaaagg gcaaactcag cttcacatgc cgctgtgata cagtggtttc gtgtgagggc 900tacgtcgtta agagaataac gatgagccca ggcctttatg gaaaaaccac agggtatgcg 960gtaacccacc acgcagacgg attcctgatg tgcaagacta ccgacacggt tgacggcgaa 1020agagtgtcat tctcggtgtg cacatacgtg ccggcgacca tttgtgatca aatgaccggc 1080atccttgcta cagaagtcac gccggaggat gcacagaagc tgttggtggg gctgaaccag 1140agaatagtgg ttaacggcag aacgcaacgg aatacgaaca ccatgaaaaa ttatctgctt 1200cccgtggtcg cccaagcctt cagtaagtgg gcaaaggagt gccggaaaga catggaagat 1260gaaaaactcc tgggggtcag agaaagaaca ctgacctgct gctgtctatg ggcattcaag 1320aagcagaaaa cacacacggt ctacaagagg cctgataccc agtcaattca gaaggttcag 1380gccgagtttg acagctttgt ggtaccgagt ctgtggtcgt ccgggttgtc aatccctttg 1440aggactagaa tcaaatggtt gttaagcaag gtgccaaaaa ccgacctgat cccatacagc 1500ggagacgccc gagaagcccg ggacgcagaa aaagaagcag aggaagaacg agaagcagaa 1560ctgactcgcg aagccctacc acctctacag gcagcacagg aagatgttca ggtcgaaatc 1620gacgtggaac agcttgagga cagagcgggc gcaggaataa tagagactcc gagaggagct 1680atcaaagtta ctgcccaacc aacagaccac gtcgtgggag agtacctggt actctccccg 1740cagaccgtac tacgtagcca gaagctcagt ctgattcacg ctttggcgga gcaagtgaag 1800acgtgcacgc acaacggacg agcagggagg tatgcggtcg aagcgtacga cggccgagtc

1860ctagtgccct caggctatgc aatctcgcct gaagacttcc agagtctaag cgaaagcgca 1920acgatggtgt ataacgaaag agagttcgta aacagaaagc tacaccatat tgcgatgcac 1980ggaccagccc tgaacaccga cgaagagtcg tatgagctgg tgagggcaga gaggacagaa 2040cacgagtacg tctacgacgt ggatcagaga agatgctgta agaaggaaga agccgcagga 2100ctggtactgg tgggcgactt gactaatccg ccctaccacg aattcgcata tgaagggcta 2160aaaatccgcc ctgcctgccc atacaaaatt gcagtcatag gagtcttcgg agtaccggga 2220tctggcaagt cagctattat caagaaccta gttaccaggc aggacctggt gactagcgga 2280aagaaagaaa actgccaaga aatcaccacc gacgtgatga gacagagagg tctagagata 2340tctgcacgta cggttgactc gctgctcttg aatggatgca acagaccagt cgacgtgttg 2400tacgtagacg aggcgtttgc gtgccactct ggaacgctac ttgctttgat cgccttggtg 2460agaccaaggc agaaagttgt actttgtggt gacccgaagc agtgcggctt cttcaatatg 2520atgcagatga aagtcaacta taatcacaac atctgcaccc aagtgtacca caaaagtatc 2580tccaggcggt gtacactgcc tgtgaccgcc attgtgtcat cgttgcatta cgaaggcaaa 2640atgcgcacta cgaatgagta caacaagccg attgtagtgg acactacagg ctcaacaaaa 2700cctgaccctg gagacctcgt gttaacgtgc ttcagagggt gggttaaaca actgcaaatt 2760gactatcgtg gatacgaggt catgacagca gccgcatccc aagggttaac cagaaaagga 2820gtttacgcag ttagacaaaa agttaatgaa aacccgctct atgcatcaac gtcagagcac 2880gtcaacgtac tcctaacgcg tacggaaggt aaactggtat ggaagacact ttccggcgac 2940ccgtggataa agacgctgca gaacccaccg aaaggaaact tcaaagcaac tattaaggag 3000tgggaggtgg agcatgcatc aataatggcg ggcatctgca gtcaccaaat gaccttcgat 3060acattccaaa ataaagccaa cgtttgttgg gctaagagct tggtccctat cctcgaaaca 3120gcggggataa aactaaatga taggcagtgg tctcagataa ttcaagcctt caaagaagac 3180aaagcatact cacctgaagt agccctgaat gaaatatgta cgcgcatgta tggggtggat 3240ctagacagcg ggctattttc taaaccgttg gtgtctgtgt attacgcgga taaccactgg 3300gataataggc ctggagggaa aatgttcgga tttaaccccg aggcagcatc cattctagaa 3360agaaagtatc cattcacaaa agggaagtgg aacatcaaca agcagatctg cgtgactacc 3420aggaggatag aagactttaa ccctaccacc aacatcatac cggccaacag gagactacca 3480cactcattag tggccgaaca ccgcccagta aaaggggaaa gaatggaatg gctggttaac 3540aagataaacg gccaccacgt gctcctggtc agtggctata accttgcact gcctactaag 3600agagtcactt gggtagcgcc gttaggtgtc cgcggagcgg actacacata caacctagag 3660ttgggtctgc cagcaacgct tggtaggtat gacctagtgg tcataaacat ccacacacct 3720tttcgcatac accattacca acagtgcgtc gaccacgcaa tgaaactgca aatgctcggg 3780ggtgactcat tgagactgct caaaccgggc ggctctctat tgatcagagc atatggttac 3840gcagatagaa ccagtgaacg agtcatctgc gtattgggac gcaagtttag atcgtctaga 3900gcgttgaaac caccatgtgt caccagcaac actgagatgt ttttcctatt cagcaacttt 3960gacaatggca gaaggaattt cacaactcat gtcatgaaca atcaactgaa tgcagccttc 4020gtaggacagg tcacccgagc aggatgtgca ccgtcgtacc gggtaaaacg catggacatc 4080gcgaagaacg atgaagagtg cgtagtcaac gccgctaacc ctcgcgggtt accgggtgac 4140ggtgtttgca aggcagtata caaaaaatgg ccggagtcct ttaagaacag tgcaacacca 4200gtgggaaccg caaaaacagt tatgtgcggt acgtatccag taatccacgc tgttggacca 4260aacttctcta attattcgga gtctgaaggg gaccgggaat tggcagctgc ctatcgagaa 4320gtcgcaaagg aagtaactag gctgggagta aatagtgtag ctatacctct cctctccaca 4380ggtgtatact caggagggaa agacaggctg acccagtcac tgaaccacct ctttacagcc 4440atggactcga cggatgcaga cgtggtcatc tactgccgcg acaaagaatg ggagaagaaa 4500atatctgagg ccatacagat gcggacccaa gtagagctgc tggatgagca catctccata 4560gactgcgata ttgttcgcgt gcaccctgac agcagcttgg caggcagaaa aggatacagc 4620accacggaag gcgcactgta ctcatatcta gaagggaccc gttttcatca gacggctgtg 4680gatatggcgg agatacatac tatgtggcca aagcaaacag aggccaatga gcaagtctgc 4740ctatatgccc tgggggaaag tattgaatcg atcaggcaga aatgcccggt ggatgatgca 4800gacgcatcat ctccccccaa aactgtcccg tgcctttgcc gttacgctat gactccagaa 4860cgcgtcaccc ggcttcgcat gaaccacgtc acaagcataa ttgtgtgttc ttcgtttccc 4920ctcccaaagt acaaaataga aggagtgcaa aaagtcaaat gctctaaggt aatgctattt 4980gaccacaacg tgccatcgcg cgtaagtcca agggaatata gatcttccca ggagtctgca 5040caggaggcga gtacaatcac gtcactgacg catagtcaat tcgacctaag cgttgatggc 5100gagatactgc ccgtcccgtc agacctggat gctgacgccc cagccctaga accagcacta 5160gacgacgggg cgacacacac gctgccatcc acaaccggaa accttgcggc cgtgtctaga 5220cagggcaggt gggtatatat tctcgtcgga caccggtcca ggtcatttac aacagaagtc 5280agtacgccag tcagtgctgc cggtgaacac cctggaggaa gtccacgagg agaagtgtta 5340cccacctaag ctggatgaag caaaggagca actattactt aagaaactcc aggagagtgc 5400atccatggcc aacagaagca ggtatcagtc gcgcaaagta gaaaacatga aagcagcaat 5460catccagaga ctaaagagag gctgtagact atacttaatg tcagagaccc caaaagtccc 5520tacttaccgg actacatatc cggcgcctgt gtactcgcct ccgatcaacg tccgattgtc 5580caatcccgag tccgcagtgg cagcatgcaa tgagttctta gctagaaact atccaactgt 5640ctcatcatac caaattaccg acgagtatga tgcatatcta gacatggtgg acgggtcgga 5700gagttgcctg gaccgagcga cattcaatcc gtcaaaactc aggagctacc cgaaacagca 5760cgcttaccac gcgccctcca tcagaagcgc tgtaccgtcc ccattccaga acacactaca 5820gaatgtactg gcagcagcca cgaaaagaaa ctgcaacgtc acacagatga gggaattacc 5880cactttggac tcagcagtat tcaacgtgga gtgtttcaaa aaattcgcat gcaaccaaga 5940atactgggaa gaatttgctg ccagccctat taggataaca actgagaatt tagcaaccta 6000tgttactaaa ctaaaagggc caaaagcagc agcgctattc gcaaaaaccc ataatctact 6060gccactacag gaagtaccaa tggataggtt cacagtagat atgaaaaggg acgtgaaggt 6120gactcctggt acaaagcata cagaggaaag acctaaggtg caggttatac aggcggctga 6180acccttggcg acagcatacc tatgtgggat tcacagagag ctggttagga ggctgaacgc 6240cgtcctccta cccaatgtac atacactatt tgacatgtct gccgaggatt tcgatgccat 6300catagccgca cactttaagc caggagacac tgttttggaa acggacatag cctcctttga 6360taagagccaa gatgattcac ttgcgcttac tgctttgatg ctgttagagg atttaggggt 6420ggatcactcc ctgctggact tgatagaggc tgctttcgga gagatttcca gctgtcacct 6480accgacaggt acgcgcttca agttcggcgc catgatgaaa tcaggtatgt tcctaactct 6540gttcgtcaac acattgttaa acatcaccat cgccagccga gtgctggaag atcgtctgac 6600aaaatccgcg tgcgcggcct tcatcggcga cgacaacata atacatggag tcgtctccga 6660tgaattgatg gcagccagat gtgccacttg gatgaacatg gaagtgaaga tcatagatgc 6720agttgtatcc ttgaaagccc cttacttttg tggagggttt atactgcacg atactgtgac 6780aggaacagct tgcagagtgg cagacccgct aaaaaggctt tttaaactgg gcaaaccgct 6840agcggcaggt gacgaacaag atgaagatag aagacgagcg ctggctgacg aagtgatcag 6900atggcaacga acagggctaa ttgatgagct ggagaaagcg gtatactcta ggtacgaagt 6960gcagggtata tcagttgtgg taatgtccat ggccaccttt gcaagctcca gatccaactt 7020cgagaagctc agaggacccg tcataacttt gtacggcggt cctaaatagg tacgcactac 7080agctacctat tttgcagaag ccgacagcaa gtatctaaac actaatcagc tacaatggag 7140ttcatcccaa cccaaacttt ttacaatagg aggtaccagc ctcgaccctg gactccgcgc 7200cctactatcc aagtcatcag gcccagaccg cgccctcaga ggcaagctgg gcaacttgcc 7260cagctgatct cagcagttaa taaactgaca atgcgcgcgg taccccaaca gaagccacgc 7320aggaatcgga agaataagaa gcaaaagcaa aaacaacagg cgccacaaaa caacacaaat 7380caaaagaagc agccacctaa aaagaaaccg gctcaaaaga aaaagaagcc gggccgcaga 7440gagaggatgt gcatgaaaat cgaaaatgat tgtattttcg aagtcaagca cgaaggtaag 7500gtaacaggtt acgcgtgcct ggtgggggac aaagtaatga aaccagcaca cgtaaagggg 7560accatcgata acgcggacct ggccaaactg gcctttaagc ggtcatctaa gtatgacctt 7620gaatgcgcgc agatacccgt gcacatgaag tccgacgctt cgaagttcac ccatgagaaa 7680ccggaggggt actacaactg gcaccacgga gcagtacagt actcaggagg ccggttcacc 7740atccctacag gtgctggcaa accaggggac agcggcagac cgatcttcga caacaaggga 7800cgcgtggtgg ccatagtctt aggaggagct aatgaaggag cccgtacagc cctctcggtg 7860gtgacctgga ataaagacat tgtcactaaa atcacccccg agggggccga agagtggagt 7920cttgccatcc cagttatgtg cctgttggca aacaccacgt tcccctgctc ccagccccct 7980tgcacgccct gctgctacga aaaggaaccg gaggaaaccc tacgcatgct tgaggacaac 8040gtcatgagac ctgggtacta tcagctgcta caagcatcct taacatgttc tccccaccgc 8100cagcgacgca gcaccaagga caacttcaat gtctataaag ccacaagacc atacttagct 8160cactgtcccg actgtggaga agggcactcg tgccatagtc ccgtagcact agaacgcatc 8220agaaatgaag cgacagacgg gacgctgaaa atccaggtct ccttgcaaat cggaataaag 8280acggatgaca gccacgattg gaccaagctg cgttatatgg acaaccacat gccagcagac 8340gcagagaggg cggggctatt tgtaagaaca tcagcaccgt gtacgattac tggaacaatg 8400ggacacttca tcctggcccg atgtccaaaa ggggaaactc tgacggtggg attcactgac 8460agtaggaaga ttagtcactc atgtacgcac ccatttcacc acgaccctcc tgtgataggt 8520cgggaaaaat tccattcccg accgcagcac ggtaaagagc taccttgcag cacgtacgtg 8580cagagcaccg ccgcaactac cgaggagata gaggtacaca tgcccccaga cacccctgat 8640cgcacattaa tgtcacaaca gtccggcaac gtaaagatca cagtcaatgg ccagacggtg 8700cggtacaagt gtaattgcgg tggctcaaat gaaggactaa caactacaga caaagtgatt 8760aataactgca aggttgatca atgtcatgcc gcggtcacca atcacaaaaa gtggcagtat 8820aactcccctc tggtcccgcg taatgctgaa cttggggacc gaaaaggaaa aattcacatc 8880ccgtttccgc tggcaaatgt aacatgcagg gtgcctaaag caaggaaccc caccgtgacg 8940tacgggaaaa accaagtcat catgctactg tatcctgacc acccaacact cctgtcctac 9000cggaatatgg gagaagaacc aaactatcaa gaagagtggg tgatgcataa gaaggaagtc 9060gtgctaaccg tgccgactga agggctcgag gtcacgtggg gcaacaacga gccgtataag 9120tattggccgc agttatctac aaacggtaca gcccatggcc acccgcatga gataattctg 9180tattattatg agctgtaccc cactatgact gtagtagttg tgtcagtggc cacgttcata 9240ctcctgtcga tggtgggtat ggcagcgggg atgtgcatgt gtgcacgacg cagatgcatc 9300acaccgtatg aactgacacc aggagctacc gtccctttcc tgcttagcct aatatgctgc 9360atcagaacag ctaaagcggc cacataccaa gaggctgcga tatacctgtg gaacgagcag 9420caacctttgt tttggctaca agcccttatt ccgctggcag ccctgattgt tctatgcaac 9480tgtctgagac tcttaccatg ctgctgtaaa acgttggctt ttttagccgt aatgagcgtc 9540ggtgcccaca ctgtgagcgc gtacgaacac gtaacagtga tcccgaacac ggtgggagta 9600ccgtataaga ctctagtcaa tagacctggc tacagcccca tggtattgga gatggaacta 9660ctgtcagtca ctttggagcc aacactatcg cttgattaca tcacgtgcga gtacaaaacc 9720gtcatcccgt ctccgtacgt gaagtgctgc ggtacagcag agtgcaagga caaaaaccta 9780cctgactaca gctgtaaggt cttcaccggc gtctacccat ttatgtgggg cggcgcctac 9840tgcttctgcg acgctgaaaa cacgcagttg agcgaagcac acgtggagaa gtccgaatca 9900tgcaaaacag aatttgcatc agcatacagg gctcataccg catctgcatc agctaagctc 9960cgcgtccttt accaaggaaa taacatcact gtaactgcct atgcaaacgg cgaccatgcc 10020gtcacagtta aggacgccaa attcattgtg gggccaatgt cttcagcctg gacacctttc 10080gacaacaaaa ttgtggtgta caaaggtgac gtctataaca tggactaccc gccctttggc 10140gcaggaagac caggacaatt tggcgatatc caaagtcgca cacctgagag taaagacgtc 10200tatgctaata cacaactggt actgcagaga ccggctgcgg gtacggtaca cgtgccatac 10260tctcaggcac catctggctt taagtattgg ctaaaagaac gcggggcgtc gctgcagcac 10320acagcaccat ttggctgcca aatagcaaca aacccggtaa gagcggtgaa ctgcgccgta 10380gggaacatgc ccatctccat cgacataccg gaagcggcct tcactagggt cgtcgacgcg 10440ccctctttaa cggacatgtc gtgcgaggta ccagcctgca cccattcctc agactttggg 10500ggcgtcgcca ttattaaata tgcagccagc aagaaaggca agtgtgcggt gcattcgatg 10560actaacgccg tcactattcg ggaagctgag atagaagttg aagggaattc tcagctgcaa 10620atctctttct cgacggcctt agccagcgcc gaattccgcg tacaagtctg ttctacacaa 10680gtacactgtg cagccgagtg ccaccccccg aaggaccaca tagtcaacta cccggcgtca 10740cataccaccc tcggggtcca ggacatctcc gctacggcga tgtcatgggt gcagaagatc 10800acgggaggtg tgggactggt tgttgctgtt gccgcactga ttctaatcgt ggtgctatgc 10860gtgtcgttca gcaggcacta acttgacaat taagtatgaa ggtatatgtg tcccctaaga 10920gacacactgt acatagcaaa taatctatag atcaaagggc tacgcaaccc ctgaatagta 10980acaaaataca aaatcactaa aaattataaa aacagaaaaa tacataaata ggtatacgtg 11040tcccctaaga gacacattgt atgtaggtga taagtataga tcaaagggcc gaataacccc 11100tgaatagtaa caaaatatga aaatcaataa aaatcataaa atagaaaaac cataaacaga 11160agtagttcaa agggctataa aacccctgaa tagtaacaaa acataaaatt aataaaaatc 11220aaatgaatac catatgg 1123771797DNAChikungunya virus 7atacccgtgc acatgaagtc cgacgcttcg aagttcaccc atgagaaacc ggaggggtac 60tacaactggc accacggagc agtacagtac tcaggaggcc ggttcaccat ccctacaggt 120gctggcaaac caggggacag cggcagaccg atcttcgaca acaagggacg cgtggtggcc 180atagtcttag gaggagctaa tgaaggagcc cgtacagccc tctcggtggt gacctggaat 240aaagacattg tcactaaaat cacccccgag ggggccgaag agtggagtct tgccatccca 300gttatgtgcc tgttggcaaa caccacgttc ccctgctccc agcccccttg cacgccctgc 360tgctacgaaa aggaaccgga ggaaacccta cgcatgcttg aggacaacgt catgagacct 420gggtactatc agctgctaca agcatcctta acatgttctc cccaccgcca gcgacgcagc 480accaaggaca acttcaatgt ctataaagcc acaagaccat acttagctca ctgtcccgac 540tgtggagaag ggcactcgtg ccatagtccc gtagcactag aacgcatcag aaatgaagcg 600acagacggga cgctgaaaat ccaggtctcc ttgcaaatcg gaataaagac ggatgacagc 660cacgattgga ccaagctgcg ttatatggac aaccacatgc cagcagacgc agagagggcg 720gggctatttg taagaacatc agcaccgtgt acgattactg gaacaatggg acacttcatc 780ctggcccgat gtccaaaagg ggaaactctg acggtgggat tcactgacag taggaagatt 840agtcactcat gtacgcaccc atttcaccac gaccctcctg tgataggtcg ggaaaaattc 900cattcccgac cgcagcacgg taaagagcta ccttgcagca cgtacgtgca gagcaccgcc 960gcaactaccg aggagataga ggtacacatg cccccagaca cccctgatcg cacattaatg 1020tcacaacagt ccggcaacgt aaagatcaca gtcaatggcc agacggtgcg gtacaagtgt 1080aattgcggtg gctcaaatga aggactaaca actacagaca aagtgattaa taactgcaag 1140gttgatcaat gtcatgccgc ggtcaccaat cacaaaaagt ggcagtataa ctcccctctg 1200gtcccgcgta atgctgaact tggggaccga aaaggaaaaa ttcacatccc gtttccgctg 1260gcaaatgtaa catgcagggt gcctaaagca aggaacccca ccgtgacgta cgggaaaaac 1320caagtcatca tgctactgta tcctgaccac ccaacactcc tgtcctaccg gaatatggga 1380gaagaaccaa actatcaaga agagtgggtg atgcataaga aggaagtcgt gctaaccgtg 1440ccgactgaag ggctcgaggt cacgtggggc aacaacgagc cgtataagta ttggccgcag 1500ttatctacaa acggtacagc ccatggccac ccgcatgaga taattctgta ttattatgag 1560ctgtacccca ctatgactgt agtagttgtg tcagtggcca cgttcatact cctgtcgatg 1620gtgggtatgg cagcggggat gtgcatgcgt gcacgacgca gatgcatcac accgtatgaa 1680ctgacaccag gagctaccgt ccctttcctg cttagcctaa tatgctgcat cagaacagct 1740aaagcggcca cataccaaga ggctgcgata tacctgtgga acgagcagca accttta 179781797DNAChikungunya virus 8atacccgtgc acatgaagtc cgacgcttcg aagttcaccc atgagaaacc ggaggggtac 60tacaactggc accacggagc agtacagtac tcaggaggcc ggttcaccat ccctacaggt 120gctggcaaac caggggacag cggcagaccg atcttcgaca acaagggacg cgtggtggcc 180atagtcttag gaggagctaa tgaaggagcc cgtacagccc tctcggtggt gacctggaat 240aaagacattg tcactaaaat cacccccgag ggggccgaag agtggagtct tgccatccca 300gttatgtgcc tgttggcaaa caccacgttc ccctgctccc agcccccttg cacgccctgc 360tgctacgaaa aggaaccgga ggaaacccta cgcatgcttg aggacaacgt catgagacct 420gggtactatc agctgctaca agcatcctta acatgttctc cccaccgcca gcgacgcagc 480accaaggaca acttcaatgt ctataaagcc acaagaccat acttagctca ctgtcccgac 540tgtggagaag ggcactcgtg ccatagtccc gtagcactag aacgcatcag aaatgaagcg 600acagacggga cgctgaaaat ccaggtctcc ttgcaaatcg gaataaagac ggatgacagc 660cacgattgga ccaagctgcg ttatatggac aaccacatgc cagcagacgc agagagggcg 720gggctatttg taagaacatc agcaccgtgt acgattactg gaacaatggg acacttcatc 780ctggcccgat gtccaaaagg ggaaactctg acggtgggat tcactgacag taggaagatt 840agtcactcat gtacgcaccc atttcaccac gaccctcctg tgataggtcg ggaaaaattc 900cattcccgac cgcagcacgg taaagagcta ccttgcagca cgtacgtgca gagcaccgcc 960gcaactaccg aggagataga ggtacacatg cccccagaca cccctgatcg cacattaatg 1020tcacaacagt ccggcaacgt aaagatcaca gtcaatggcc agacggtgcg gtacaagtgt 1080aattgcggtg gctcaaatga aggactaaca actacagaca aagtgattaa taactgcaag 1140gttgatcaat gtcatgccgc ggtcaccaat cacaaaaagt ggcagtataa ctcccctctg 1200gtcccgcgta atgctgaact tggggaccga aaaggaaaaa ttcacatccc gtttccgctg 1260gcaaatgtaa catgcagggt gcctaaagca aggaacccca ccgtgacgta cgggaaaaac 1320caagtcatca tgctactgta tcctgaccac ccaacactcc tgtcctaccg gaatatggga 1380gaagaaccaa actatcaaga agagtgggtg atgcataaga aggaagtcgt gctaaccgtg 1440ccgactgaag ggctcgaggt cacgtggggc aacaacgagc cgtataagta ttggccgcag 1500ttatctacaa acggtacagc ccatggccac ccgcatgaga taattctgta ttattatgag 1560ctgtacccca ctatgactgt agtagttgtg tcagtggcca cgttcatact cctgtcgatg 1620gtgggtatgg cagcggggat gtgcatgtgt gcacgacgca gatgcatcac accgtatgaa 1680ctgacaccag gagctaccgt ccctttcctg cttagcctaa tatgctgcat cagaacagct 1740aaagcggcca cataccaaga ggctgcgata tacctgtgga acgagcagca accttta 179791797DNAChikungunya virus 9atacccgtgc acatgaagtc cgacgcttcg aagttcaccc atgagaaacc ggaggggtac 60tacaactggc accacggagc agtacagtac tcaggaggcc ggttcaccat ccctacaggt 120gctggcaaac caggggacag cggcagaccg atcttcgaca acaagggacg cgtggtggcc 180atagtcttag gaggagctaa tgaaggagcc cgtacagccc tctcggtggt gacctggaat 240aaagacattg tcactaaaat cacccccgag ggggccgaag agtggagtct tgccatccca 300gttatgtgcc tgttggcaaa caccacgttc ccctgctccc agcccccttg cacgccctgc 360tgctacgaaa aggaaccgga ggaaacccta cgcatgcttg aggacaacgt catgagacct 420gggtactatc agctgctaca agcatcctta acatgttctc cccaccgcca gcgacgcagc 480accaaggaca acttcaatgt ctataaagcc acaagaccat acttagctca ctgtcccgac 540tgtggagaag ggcactcgtg ccatagtccc gtagcactag aacgcatcag aaatgaagcg 600acagacggga cgctgaaaat ccaggtctcc ttgcaaatcg gaataaagac ggatgacagc 660cacgattgga ccaagctgcg ttatatggac aaccacatgc cagcagacgc agagagggcg 720gggctatttg taagaacatc agcaccgtgt acgattactg gaacaatggg acacttcatc 780ctggcccgat gtccaaaagg ggaaactctg acggtgggat tcactgacag taggaagatt 840agtcactcat gtacgcaccc atttcaccac gaccctcctg tgataggtcg ggaaaaattc 900cattcccgac cgcagcacgg taaagagcta ccttgcagca cgtacgtgca gagcaccgcc 960gcaactaccg aggagataga ggtacacatg cccccagaca cccctgatcg cacattaatg 1020tcacaacagt ccggcaacgt aaagatcaca gtcaatggcc agacggtgcg gtacaagtgt 1080aattgcggtg gctcaaatga aggactaaca actacagaca aagtgattaa taactgcaag 1140gttgatcaat gtcatgccgc ggtcaccaat cacaaaaagt ggcagtataa ctcccctctg 1200gtcccgcgta atgctgaact tggggaccga aaaggaaaaa ttcacatccc gtttccgctg 1260gcaaatgtaa catgcagggt gcctaaagca aggaacccca ccgtgacgta cgggaaaaac 1320caagtcatca tgctactgta tcctgaccac ccaacactcc tgtcctaccg gaatatggga 1380gaagaaccaa actatcaaga agagtgggtg atgcataaga aggaagtcgt gctaaccgtg 1440ccgactgaag ggctcgaggt cacgtggggc aacaacgagc cgtataagta ttggccgcag 1500ttatctacaa acggtacagc ccatggccac ccgcacgaga taattctgta ttattatgag 1560ctgtacccca ctatgactgt agtagttgtg tcagtggcca cgttcatact cctgtcgatg 1620gtgggtatgg cagcggggat gtgcatgtgt gcacgacgca gatgcatcac accgtatgaa 1680ctgacaccag gagctaccgt ccctttcctg cttagcctaa tatgctgcat cagaacagct 1740aaagcggcca cataccaaga ggctgcgata tacctgtgga acgagcagca accttta 1797101797DNAChikungunya virus 10atacccgtgc acatgaagtc cgacgcttcg aagttcaccc atgagaaacc ggaggggtac 60tacaactggc accacggagc agtacagtac tcaggaggcc ggttcaccat ccctacaggt

120gctggcaaac caggggacag cggcagaccg atcttcgaca acaagggacg cgtggtggcc 180atagtcttag gaggagctaa tgaaggagcc cgtacagccc tctcggtggt gacctggaat 240aaagacattg tcactaaaat cacccccgag ggggccgaag agtggagtct tgccatccca 300gttatgtgcc tgttggcaaa caccacgttc ccctgctccc agcccccttg cacgccctgc 360tgctacgaaa aggaaccgga ggaaacccta cgcatgcttg aggacaacgt catgagacct 420gggtactatc agctgctaca agcatcctta acatgttctc cccaccgcca gcgacgcagc 480accaaggaca acttcaatgt ctataaagcc acaagaccat acttagctca ctgtcccgac 540tgtggagaag ggcactcgtg ccatagtccc gtagcactag aacgcatcag aaatgaagcg 600acagacggga cgctgaaaat ccaggtctcc ttgcaaatcg gaataaagac ggatgacagc 660cacgattgga ccaagctgcg ttatatggac aaccacatgc cagcagacgc agagagggcg 720gggctatttg taagaacatc agcaccgtgt acgattactg gaacaatggg acacttcatc 780ctggcccgat gtccaaaagg ggaaactctg acggtgggat tcactgacag taggaagatt 840agtcactcat gtacgcaccc atttcaccac gaccctcctg tgataggtcg ggaaaaattc 900cattcccgac cgcagcacgg taaagagata ccttgcagca cgtacgtgca gagcaccgcc 960gcaactaccg aggagataga ggtacacatg cccccagaca cccctgatcg cacattaatg 1020tcacaacagt ccggcaacgt aaagatcaca gtcaatggcc agacggtgcg gtacaagtgt 1080aattgcggtg gctcaaatga aggactaaca actacagaca aagtgattaa taactgcaag 1140gttgatcaat gtcatgccgc ggtcaccaat cacaaaaagt ggcagtataa ctcccctctg 1200gtcccgcgta atgctgaact tggggaccga aaaggaaaaa ttcacatccc gtttccgctg 1260gcaaatgtaa catgcagggt gcctaaagca aggaacccca ccgtgacgta cgggaaaaac 1320caagtcatca tgctactgta tcctgaccac ccaacactcc tgtcctaccg gaatatggga 1380gaagaaccaa actatcaaga agagtgggtg atgcataaga aggaagtcgt gctaaccgtg 1440ccgactgaag ggctcgaggt cacgtggggc aacaacgagc cgtataagta ttggccgcag 1500ttatctacaa acggtacagc ccatggccac ccgcatgaga taattctgta ttattatgag 1560ctgtacccca ctatgactgt agtagttgtg tcagtggcca cgttcatact cctgtcgatg 1620gtgggtatgg cagcggggat gtgcatgtgt gcacgacgca gatgcatcac accgtatgaa 1680ctgacaccag gagctaccgt ccctttcctg cttagcctaa tatgctgcat cagaacagct 1740aaagcggcca cataccaaga ggctgcgata tacctgtgga acgagcagca accttta 1797111092DNAChikungunya virus 11gacaacttca atgtctataa agccacaaga ccatacttag ctcactgtcc cgactgtgga 60gaagggcact cgtgccatag tcccgtagca ctagaacgca tcagaaatga agcgacagac 120gggacgctga aaatccaggt ctccttgcaa atcggaataa agacggatga cagccacgat 180tggaccaagc tgcgttatat ggacaaccac atgccagcag acgcagagag ggcggggcta 240tttgtaagaa catcagcacc gtgtacgatt actggaacaa tgggacactt catcctggcc 300cgatgtccaa aaggggaaac tctgacggtg ggattcactg acagtaggaa gattagtcac 360tcatgtacgc acccatttca ccacgaccct cctgtgatag gtcgggaaaa attccattcc 420cgaccgcagc acggtaaaga gctaccttgc agcacgtacg tgcagagcac cgccgcaact 480accgaggaga tagaggtaca catgccccca gacacccctg atcgcacatt aatgtcacaa 540cagtccggca acgtaaagat cacagtcaat ggccagacgg tgcggtacaa gtgtaattgc 600ggtggctcaa atgaaggact aacaactaca gacaaagtga ttaataactg caaggttgat 660caatgtcatg ccgcggtcac caatcacaaa aagtggcagt ataactcccc tctggtcccg 720cgtaatgctg aacttgggga ccgaaaagga aaaattcaca tcccgtttcc gctggcaaat 780gtaacatgca gggtgcctaa agcaaggaac cccaccgtga cgtacgggaa aaaccaagtc 840atcatgctac tgtatcctga ccacccaaca ctcctgtcct accggaatat gggagaagaa 900ccaaactatc aagaagagtg ggtgatgcat aagaaggaag tcgtgctaac cgtgccgact 960gaagggctcg aggtcacgtg gggcaacaac gagccgtata agtattggcc gcagttatct 1020acaaacggta cagcccatgg ccacccgcat gagataattc tgtattatta tgagctgtac 1080cccactatga ct 1092121092DNAChikungunya virus 12gacaacttca atgtctataa agccacaaga ccatacttag ctcactgtcc cgactgtgga 60gaagggcact cgtgccatag tcccgtagca ctagaacgca tcagaaatga agcgacagac 120gggacgctga aaatccaggt ctccttgcaa atcggaataa agacggatga cagccacgat 180tggaccaagc tgcgttatat ggacaaccac atgccagcag acgcagagag ggcggggcta 240tttgtaagaa catcagcacc gtgtacgatt actggaacaa tgggacactt catcctggcc 300cgatgtccaa aaggggaaac tctgacggtg ggattcactg acagtaggaa gattagtcac 360tcatgtacgc acccatttca ccacgaccct cctgtgatag gtcgggaaaa attccattcc 420cgaccgcagc acggtaaaga gctaccttgc agcacgtacg tgcagagcac cgccgcaact 480accgaggaga tagaggtaca catgccccca gacacccctg atcgcacatt aatgtcacaa 540cagtccggca acgtaaagat cacagtcaat ggccagacgg tgcggtacaa gtgtaattgc 600ggtggctcaa atgaaggact aacaactaca gacaaagtga ttaataactg caaggttgat 660caatgtcatg ccgcggtcac caatcacaaa aagtggcagt ataactcccc tctggtcccg 720cgtaatgctg aacttgggga ccgaaaagga aaaattcaca tcccgtttcc gctggcaaat 780gtaacatgca gggtgcctaa agcaaggaac cccaccgtga cgtacgggaa aaaccaagtc 840atcatgctac tgtatcctga ccacccaaca ctcctgtcct accggaatat gggagaagaa 900ccaaactatc aagaagagtg ggtgatgcat aagaaggaag tcgtgctaac cgtgccgact 960gaagggctcg aggtcacgtg gggcaacaac gagccgtata agtattggcc gcagttatct 1020acaaacggta cagcccatgg ccacccgcat gagataattc tgtattatta tgagctgtac 1080cccactatga ct 1092131092DNAChikungunya virus 13gacaacttca atgtctataa agccacaaga ccatacttag ctcactgtcc cgactgtgga 60gaagggcact cgtgccatag tcccgtagca ctagaacgca tcagaaatga agcgacagac 120gggacgctga aaatccaggt ctccttgcaa atcggaataa agacggatga cagccacgat 180tggaccaagc tgcgttatat ggacaaccac atgccagcag acgcagagag ggcggggcta 240tttgtaagaa catcagcacc gtgtacgatt actggaacaa tgggacactt catcctggcc 300cgatgtccaa aaggggaaac tctgacggtg ggattcactg acagtaggaa gattagtcac 360tcatgtacgc acccatttca ccacgaccct cctgtgatag gtcgggaaaa attccattcc 420cgaccgcagc acggtaaaga gctaccttgc agcacgtacg tgcagagcac cgccgcaact 480accgaggaga tagaggtaca catgccccca gacacccctg atcgcacatt aatgtcacaa 540cagtccggca acgtaaagat cacagtcaat ggccagacgg tgcggtacaa gtgtaattgc 600ggtggctcaa atgaaggact aacaactaca gacaaagtga ttaataactg caaggttgat 660caatgtcatg ccgcggtcac caatcacaaa aagtggcagt ataactcccc tctggtcccg 720cgtaatgctg aacttgggga ccgaaaagga aaaattcaca tcccgtttcc gctggcaaat 780gtaacatgca gggtgcctaa agcaaggaac cccaccgtga cgtacgggaa aaaccaagtc 840atcatgctac tgtatcctga ccacccaaca ctcctgtcct accggaatat gggagaagaa 900ccaaactatc aagaagagtg ggtgatgcat aagaaggaag tcgtgctaac cgtgccgact 960gaagggctcg aggtcacgtg gggcaacaac gagccgtata agtattggcc gcagttatct 1020acaaacggta cagcccatgg ccacccgcac gagataattc tgtattatta tgagctgtac 1080cccactatga ct 1092141092DNAChikungunya virus 14gacaacttca atgtctataa agccacaaga ccatacttag ctcactgtcc cgactgtgga 60gaagggcact cgtgccatag tcccgtagca ctagaacgca tcagaaatga agcgacagac 120gggacgctga aaatccaggt ctccttgcaa atcggaataa agacggatga cagccacgat 180tggaccaagc tgcgttatat ggacaaccac atgccagcag acgcagagag ggcggggcta 240tttgtaagaa catcagcacc gtgtacgatt actggaacaa tgggacactt catcctggcc 300cgatgtccaa aaggggaaac tctgacggtg ggattcactg acagtaggaa gattagtcac 360tcatgtacgc acccatttca ccacgaccct cctgtgatag gtcgggaaaa attccattcc 420cgaccgcagc acggtaaaga gataccttgc agcacgtacg tgcagagcac cgccgcaact 480accgaggaga tagaggtaca catgccccca gacacccctg atcgcacatt aatgtcacaa 540cagtccggca acgtaaagat cacagtcaat ggccagacgg tgcggtacaa gtgtaattgc 600ggtggctcaa atgaaggact aacaactaca gacaaagtga ttaataactg caaggttgat 660caatgtcatg ccgcggtcac caatcacaaa aagtggcagt ataactcccc tctggtcccg 720cgtaatgctg aacttgggga ccgaaaagga aaaattcaca tcccgtttcc gctggcaaat 780gtaacatgca gggtgcctaa agcaaggaac cccaccgtga cgtacgggaa aaaccaagtc 840atcatgctac tgtatcctga ccacccaaca ctcctgtcct accggaatat gggagaagaa 900ccaaactatc aagaagagtg ggtgatgcat aagaaggaag tcgtgctaac cgtgccgact 960gaagggctcg aggtcacgtg gggcaacaac gagccgtata agtattggcc gcagttatct 1020acaaacggta cagcccatgg ccacccgcat gagataattc tgtattatta tgagctgtac 1080cccactatga ct 109215599PRTChikungunya virus 15Ile Pro Val His Met Lys Ser Asp Ala Ser Lys Phe Thr His Glu Lys1 5 10 15Pro Glu Gly Tyr Tyr Asn Trp His His Gly Ala Val Gln Tyr Ser Gly 20 25 30Gly Arg Phe Thr Ile Pro Thr Gly Ala Gly Lys Pro Gly Asp Ser Gly 35 40 45Arg Pro Ile Phe Asp Asn Lys Gly Arg Val Val Ala Ile Val Leu Gly 50 55 60Gly Ala Asn Glu Gly Ala Arg Thr Ala Leu Ser Val Val Thr Trp Asn65 70 75 80Lys Asp Ile Val Thr Lys Ile Thr Pro Glu Gly Ala Glu Glu Trp Ser 85 90 95Leu Ala Ile Pro Val Met Cys Leu Leu Ala Asn Thr Thr Phe Pro Cys 100 105 110Ser Gln Pro Pro Cys Thr Pro Cys Cys Tyr Glu Lys Glu Pro Glu Glu 115 120 125Thr Leu Arg Met Leu Glu Asp Asn Val Met Arg Pro Gly Tyr Tyr Gln 130 135 140Leu Leu Gln Ala Ser Leu Thr Cys Ser Pro His Arg Gln Arg Arg Ser145 150 155 160Thr Lys Asp Asn Phe Asn Val Tyr Lys Ala Thr Arg Pro Tyr Leu Ala 165 170 175His Cys Pro Asp Cys Gly Glu Gly His Ser Cys His Ser Pro Val Ala 180 185 190Leu Glu Arg Ile Arg Asn Glu Ala Thr Asp Gly Thr Leu Lys Ile Gln 195 200 205Val Ser Leu Gln Ile Gly Ile Lys Thr Asp Asp Ser His Asp Trp Thr 210 215 220Lys Leu Arg Tyr Met Asp Asn His Met Pro Ala Asp Ala Glu Arg Ala225 230 235 240Gly Leu Phe Val Arg Thr Ser Ala Pro Cys Thr Ile Thr Gly Thr Met 245 250 255Gly His Phe Ile Leu Ala Arg Cys Pro Lys Gly Glu Thr Leu Thr Val 260 265 270Gly Phe Thr Asp Ser Arg Lys Ile Ser His Ser Cys Thr His Pro Phe 275 280 285His His Asp Pro Pro Val Ile Gly Arg Glu Lys Phe His Ser Arg Pro 290 295 300Gln His Gly Lys Glu Leu Pro Cys Ser Thr Tyr Val Gln Ser Thr Ala305 310 315 320Ala Thr Thr Glu Glu Ile Glu Val His Met Pro Pro Asp Thr Pro Asp 325 330 335Arg Thr Leu Met Ser Gln Gln Ser Gly Asn Val Lys Ile Thr Val Asn 340 345 350Gly Gln Thr Val Arg Tyr Lys Cys Asn Cys Gly Gly Ser Asn Glu Gly 355 360 365Leu Thr Thr Thr Asp Lys Val Ile Asn Asn Cys Lys Val Asp Gln Cys 370 375 380His Ala Ala Val Thr Asn His Lys Lys Trp Gln Tyr Asn Ser Pro Leu385 390 395 400Val Pro Arg Asn Ala Glu Leu Gly Asp Arg Lys Gly Lys Ile His Ile 405 410 415Pro Phe Pro Leu Ala Asn Val Thr Cys Arg Val Pro Lys Ala Arg Asn 420 425 430Pro Thr Val Thr Tyr Gly Lys Asn Gln Val Ile Met Leu Leu Tyr Pro 435 440 445Asp His Pro Thr Leu Leu Ser Tyr Arg Asn Met Gly Glu Glu Pro Asn 450 455 460Tyr Gln Glu Glu Trp Val Met His Lys Lys Glu Val Val Leu Thr Val465 470 475 480Pro Thr Glu Gly Leu Glu Val Thr Trp Gly Asn Asn Glu Pro Tyr Lys 485 490 495Tyr Trp Pro Gln Leu Ser Thr Asn Gly Thr Ala His Gly His Pro His 500 505 510Glu Ile Ile Leu Tyr Tyr Tyr Glu Leu Tyr Pro Thr Met Thr Val Val 515 520 525Val Val Ser Val Ala Thr Phe Ile Leu Leu Ser Met Val Gly Met Ala 530 535 540Ala Gly Met Cys Met Arg Ala Arg Arg Arg Cys Ile Thr Pro Tyr Glu545 550 555 560Leu Thr Pro Gly Ala Thr Val Pro Phe Leu Leu Ser Leu Ile Cys Cys 565 570 575Ile Arg Thr Ala Lys Ala Ala Thr Tyr Gln Glu Ala Ala Ile Tyr Leu 580 585 590Trp Asn Glu Gln Gln Pro Leu 59516599PRTChikungunya virus 16Ile Pro Val His Met Lys Ser Asp Ala Ser Lys Phe Thr His Glu Lys1 5 10 15Pro Glu Gly Tyr Tyr Asn Trp His His Gly Ala Val Gln Tyr Ser Gly 20 25 30Gly Arg Phe Thr Ile Pro Thr Gly Ala Gly Lys Pro Gly Asp Ser Gly 35 40 45Arg Pro Ile Phe Asp Asn Lys Gly Arg Val Val Ala Ile Val Leu Gly 50 55 60Gly Ala Asn Glu Gly Ala Arg Thr Ala Leu Ser Val Val Thr Trp Asn65 70 75 80Lys Asp Ile Val Thr Lys Ile Thr Pro Glu Gly Ala Glu Glu Trp Ser 85 90 95Leu Ala Ile Pro Val Met Cys Leu Leu Ala Asn Thr Thr Phe Pro Cys 100 105 110Ser Gln Pro Pro Cys Thr Pro Cys Cys Tyr Glu Lys Glu Pro Glu Glu 115 120 125Thr Leu Arg Met Leu Glu Asp Asn Val Met Arg Pro Gly Tyr Tyr Gln 130 135 140Leu Leu Gln Ala Ser Leu Thr Cys Ser Pro His Arg Gln Arg Arg Ser145 150 155 160Thr Lys Asp Asn Phe Asn Val Tyr Lys Ala Thr Arg Pro Tyr Leu Ala 165 170 175His Cys Pro Asp Cys Gly Glu Gly His Ser Cys His Ser Pro Val Ala 180 185 190Leu Glu Arg Ile Arg Asn Glu Ala Thr Asp Gly Thr Leu Lys Ile Gln 195 200 205Val Ser Leu Gln Ile Gly Ile Lys Thr Asp Asp Ser His Asp Trp Thr 210 215 220Lys Leu Arg Tyr Met Asp Asn His Met Pro Ala Asp Ala Glu Arg Ala225 230 235 240Gly Leu Phe Val Arg Thr Ser Ala Pro Cys Thr Ile Thr Gly Thr Met 245 250 255Gly His Phe Ile Leu Ala Arg Cys Pro Lys Gly Glu Thr Leu Thr Val 260 265 270Gly Phe Thr Asp Ser Arg Lys Ile Ser His Ser Cys Thr His Pro Phe 275 280 285His His Asp Pro Pro Val Ile Gly Arg Glu Lys Phe His Ser Arg Pro 290 295 300Gln His Gly Lys Glu Leu Pro Cys Ser Thr Tyr Val Gln Ser Thr Ala305 310 315 320Ala Thr Thr Glu Glu Ile Glu Val His Met Pro Pro Asp Thr Pro Asp 325 330 335Arg Thr Leu Met Ser Gln Gln Ser Gly Asn Val Lys Ile Thr Val Asn 340 345 350Gly Gln Thr Val Arg Tyr Lys Cys Asn Cys Gly Gly Ser Asn Glu Gly 355 360 365Leu Thr Thr Thr Asp Lys Val Ile Asn Asn Cys Lys Val Asp Gln Cys 370 375 380His Ala Ala Val Thr Asn His Lys Lys Trp Gln Tyr Asn Ser Pro Leu385 390 395 400Val Pro Arg Asn Ala Glu Leu Gly Asp Arg Lys Gly Lys Ile His Ile 405 410 415Pro Phe Pro Leu Ala Asn Val Thr Cys Arg Val Pro Lys Ala Arg Asn 420 425 430Pro Thr Val Thr Tyr Gly Lys Asn Gln Val Ile Met Leu Leu Tyr Pro 435 440 445Asp His Pro Thr Leu Leu Ser Tyr Arg Asn Met Gly Glu Glu Pro Asn 450 455 460Tyr Gln Glu Glu Trp Val Met His Lys Lys Glu Val Val Leu Thr Val465 470 475 480Pro Thr Glu Gly Leu Glu Val Thr Trp Gly Asn Asn Glu Pro Tyr Lys 485 490 495Tyr Trp Pro Gln Leu Ser Thr Asn Gly Thr Ala His Gly His Pro His 500 505 510Glu Ile Ile Leu Tyr Tyr Tyr Glu Leu Tyr Pro Thr Met Thr Val Val 515 520 525Val Val Ser Val Ala Thr Phe Ile Leu Leu Ser Met Val Gly Met Ala 530 535 540Ala Gly Met Cys Met Cys Ala Arg Arg Arg Cys Ile Thr Pro Tyr Glu545 550 555 560Leu Thr Pro Gly Ala Thr Val Pro Phe Leu Leu Ser Leu Ile Cys Cys 565 570 575Ile Arg Thr Ala Lys Ala Ala Thr Tyr Gln Glu Ala Ala Ile Tyr Leu 580 585 590Trp Asn Glu Gln Gln Pro Leu 59517599PRTChikungunya virus 17Ile Pro Val His Met Lys Ser Asp Ala Ser Lys Phe Thr His Glu Lys1 5 10 15Pro Glu Gly Tyr Tyr Asn Trp His His Gly Ala Val Gln Tyr Ser Gly 20 25 30Gly Arg Phe Thr Ile Pro Thr Gly Ala Gly Lys Pro Gly Asp Ser Gly 35 40 45Arg Pro Ile Phe Asp Asn Lys Gly Arg Val Val Ala Ile Val Leu Gly 50 55 60Gly Ala Asn Glu Gly Ala Arg Thr Ala Leu Ser Val Val Thr Trp Asn65 70 75 80Lys Asp Ile Val Thr Lys Ile Thr Pro Glu Gly Ala Glu Glu Trp Ser 85 90 95Leu Ala Ile Pro Val Met Cys Leu Leu Ala Asn Thr Thr Phe Pro Cys 100 105 110Ser Gln Pro Pro Cys Thr Pro Cys Cys Tyr Glu Lys Glu Pro Glu Glu 115 120 125Thr Leu Arg Met Leu Glu Asp Asn Val Met Arg Pro Gly Tyr Tyr Gln 130 135 140Leu Leu Gln Ala Ser Leu Thr Cys Ser Pro His Arg Gln Arg Arg Ser145 150 155 160Thr Lys Asp Asn Phe Asn Val Tyr Lys Ala Thr Arg Pro Tyr Leu Ala 165 170 175His Cys Pro Asp Cys Gly Glu Gly His Ser Cys His Ser Pro Val Ala 180 185 190Leu Glu Arg Ile Arg Asn Glu Ala Thr Asp Gly Thr Leu Lys Ile Gln 195 200 205Val Ser Leu Gln Ile Gly Ile Lys Thr Asp Asp Ser His Asp Trp Thr 210 215

220Lys Leu Arg Tyr Met Asp Asn His Met Pro Ala Asp Ala Glu Arg Ala225 230 235 240Gly Leu Phe Val Arg Thr Ser Ala Pro Cys Thr Ile Thr Gly Thr Met 245 250 255Gly His Phe Ile Leu Ala Arg Cys Pro Lys Gly Glu Thr Leu Thr Val 260 265 270Gly Phe Thr Asp Ser Arg Lys Ile Ser His Ser Cys Thr His Pro Phe 275 280 285His His Asp Pro Pro Val Ile Gly Arg Glu Lys Phe His Ser Arg Pro 290 295 300Gln His Gly Lys Glu Leu Pro Cys Ser Thr Tyr Val Gln Ser Thr Ala305 310 315 320Ala Thr Thr Glu Glu Ile Glu Val His Met Pro Pro Asp Thr Pro Asp 325 330 335Arg Thr Leu Met Ser Gln Gln Ser Gly Asn Val Lys Ile Thr Val Asn 340 345 350Gly Gln Thr Val Arg Tyr Lys Cys Asn Cys Gly Gly Ser Asn Glu Gly 355 360 365Leu Thr Thr Thr Asp Lys Val Ile Asn Asn Cys Lys Val Asp Gln Cys 370 375 380His Ala Ala Val Thr Asn His Lys Lys Trp Gln Tyr Asn Ser Pro Leu385 390 395 400Val Pro Arg Asn Ala Glu Leu Gly Asp Arg Lys Gly Lys Ile His Ile 405 410 415Pro Phe Pro Leu Ala Asn Val Thr Cys Arg Val Pro Lys Ala Arg Asn 420 425 430Pro Thr Val Thr Tyr Gly Lys Asn Gln Val Ile Met Leu Leu Tyr Pro 435 440 445Asp His Pro Thr Leu Leu Ser Tyr Arg Asn Met Gly Glu Glu Pro Asn 450 455 460Tyr Gln Glu Glu Trp Val Met His Lys Lys Glu Val Val Leu Thr Val465 470 475 480Pro Thr Glu Gly Leu Glu Val Thr Trp Gly Asn Asn Glu Pro Tyr Lys 485 490 495Tyr Trp Pro Gln Leu Ser Thr Asn Gly Thr Ala His Gly His Pro His 500 505 510Glu Ile Ile Leu Tyr Tyr Tyr Glu Leu Tyr Pro Thr Met Thr Val Val 515 520 525Val Val Ser Val Ala Thr Phe Ile Leu Leu Ser Met Val Gly Met Ala 530 535 540Ala Gly Met Cys Met Cys Ala Arg Arg Arg Cys Ile Thr Pro Tyr Glu545 550 555 560Leu Thr Pro Gly Ala Thr Val Pro Phe Leu Leu Ser Leu Ile Cys Cys 565 570 575Ile Arg Thr Ala Lys Ala Ala Thr Tyr Gln Glu Ala Ala Ile Tyr Leu 580 585 590Trp Asn Glu Gln Gln Pro Leu 59518599PRTChikungunya virus 18Ile Pro Val His Met Lys Ser Asp Ala Ser Lys Phe Thr His Glu Lys1 5 10 15Pro Glu Gly Tyr Tyr Asn Trp His His Gly Ala Val Gln Tyr Ser Gly 20 25 30Gly Arg Phe Thr Ile Pro Thr Gly Ala Gly Lys Pro Gly Asp Ser Gly 35 40 45Arg Pro Ile Phe Asp Asn Lys Gly Arg Val Val Ala Ile Val Leu Gly 50 55 60Gly Ala Asn Glu Gly Ala Arg Thr Ala Leu Ser Val Val Thr Trp Asn65 70 75 80Lys Asp Ile Val Thr Lys Ile Thr Pro Glu Gly Ala Glu Glu Trp Ser 85 90 95Leu Ala Ile Pro Val Met Cys Leu Leu Ala Asn Thr Thr Phe Pro Cys 100 105 110Ser Gln Pro Pro Cys Thr Pro Cys Cys Tyr Glu Lys Glu Pro Glu Glu 115 120 125Thr Leu Arg Met Leu Glu Asp Asn Val Met Arg Pro Gly Tyr Tyr Gln 130 135 140Leu Leu Gln Ala Ser Leu Thr Cys Ser Pro His Arg Gln Arg Arg Ser145 150 155 160Thr Lys Asp Asn Phe Asn Val Tyr Lys Ala Thr Arg Pro Tyr Leu Ala 165 170 175His Cys Pro Asp Cys Gly Glu Gly His Ser Cys His Ser Pro Val Ala 180 185 190Leu Glu Arg Ile Arg Asn Glu Ala Thr Asp Gly Thr Leu Lys Ile Gln 195 200 205Val Ser Leu Gln Ile Gly Ile Lys Thr Asp Asp Ser His Asp Trp Thr 210 215 220Lys Leu Arg Tyr Met Asp Asn His Met Pro Ala Asp Ala Glu Arg Ala225 230 235 240Gly Leu Phe Val Arg Thr Ser Ala Pro Cys Thr Ile Thr Gly Thr Met 245 250 255Gly His Phe Ile Leu Ala Arg Cys Pro Lys Gly Glu Thr Leu Thr Val 260 265 270Gly Phe Thr Asp Ser Arg Lys Ile Ser His Ser Cys Thr His Pro Phe 275 280 285His His Asp Pro Pro Val Ile Gly Arg Glu Lys Phe His Ser Arg Pro 290 295 300Gln His Gly Lys Glu Ile Pro Cys Ser Thr Tyr Val Gln Ser Thr Ala305 310 315 320Ala Thr Thr Glu Glu Ile Glu Val His Met Pro Pro Asp Thr Pro Asp 325 330 335Arg Thr Leu Met Ser Gln Gln Ser Gly Asn Val Lys Ile Thr Val Asn 340 345 350Gly Gln Thr Val Arg Tyr Lys Cys Asn Cys Gly Gly Ser Asn Glu Gly 355 360 365Leu Thr Thr Thr Asp Lys Val Ile Asn Asn Cys Lys Val Asp Gln Cys 370 375 380His Ala Ala Val Thr Asn His Lys Lys Trp Gln Tyr Asn Ser Pro Leu385 390 395 400Val Pro Arg Asn Ala Glu Leu Gly Asp Arg Lys Gly Lys Ile His Ile 405 410 415Pro Phe Pro Leu Ala Asn Val Thr Cys Arg Val Pro Lys Ala Arg Asn 420 425 430Pro Thr Val Thr Tyr Gly Lys Asn Gln Val Ile Met Leu Leu Tyr Pro 435 440 445Asp His Pro Thr Leu Leu Ser Tyr Arg Asn Met Gly Glu Glu Pro Asn 450 455 460Tyr Gln Glu Glu Trp Val Met His Lys Lys Glu Val Val Leu Thr Val465 470 475 480Pro Thr Glu Gly Leu Glu Val Thr Trp Gly Asn Asn Glu Pro Tyr Lys 485 490 495Tyr Trp Pro Gln Leu Ser Thr Asn Gly Thr Ala His Gly His Pro His 500 505 510Glu Ile Ile Leu Tyr Tyr Tyr Glu Leu Tyr Pro Thr Met Thr Val Val 515 520 525Val Val Ser Val Ala Thr Phe Ile Leu Leu Ser Met Val Gly Met Ala 530 535 540Ala Gly Met Cys Met Cys Ala Arg Arg Arg Cys Ile Thr Pro Tyr Glu545 550 555 560Leu Thr Pro Gly Ala Thr Val Pro Phe Leu Leu Ser Leu Ile Cys Cys 565 570 575Ile Arg Thr Ala Lys Ala Ala Thr Tyr Gln Glu Ala Ala Ile Tyr Leu 580 585 590Trp Asn Glu Gln Gln Pro Leu 59519364PRTChikungunya virus 19Asp Asn Phe Asn Val Tyr Lys Ala Thr Arg Pro Tyr Leu Ala His Cys1 5 10 15Pro Asp Cys Gly Glu Gly His Ser Cys His Ser Pro Val Ala Leu Glu 20 25 30Arg Ile Arg Asn Glu Ala Thr Asp Gly Thr Leu Lys Ile Gln Val Ser 35 40 45Leu Gln Ile Gly Ile Lys Thr Asp Asp Ser His Asp Trp Thr Lys Leu 50 55 60Arg Tyr Met Asp Asn His Met Pro Ala Asp Ala Glu Arg Ala Gly Leu65 70 75 80Phe Val Arg Thr Ser Ala Pro Cys Thr Ile Thr Gly Thr Met Gly His 85 90 95Phe Ile Leu Ala Arg Cys Pro Lys Gly Glu Thr Leu Thr Val Gly Phe 100 105 110Thr Asp Ser Arg Lys Ile Ser His Ser Cys Thr His Pro Phe His His 115 120 125Asp Pro Pro Val Ile Gly Arg Glu Lys Phe His Ser Arg Pro Gln His 130 135 140Gly Lys Glu Leu Pro Cys Ser Thr Tyr Val Gln Ser Thr Ala Ala Thr145 150 155 160Thr Glu Glu Ile Glu Val His Met Pro Pro Asp Thr Pro Asp Arg Thr 165 170 175Leu Met Ser Gln Gln Ser Gly Asn Val Lys Ile Thr Val Asn Gly Gln 180 185 190Thr Val Arg Tyr Lys Cys Asn Cys Gly Gly Ser Asn Glu Gly Leu Thr 195 200 205Thr Thr Asp Lys Val Ile Asn Asn Cys Lys Val Asp Gln Cys His Ala 210 215 220Ala Val Thr Asn His Lys Lys Trp Gln Tyr Asn Ser Pro Leu Val Pro225 230 235 240Arg Asn Ala Glu Leu Gly Asp Arg Lys Gly Lys Ile His Ile Pro Phe 245 250 255Pro Leu Ala Asn Val Thr Cys Arg Val Pro Lys Ala Arg Asn Pro Thr 260 265 270Val Thr Tyr Gly Lys Asn Gln Val Ile Met Leu Leu Tyr Pro Asp His 275 280 285Pro Thr Leu Leu Ser Tyr Arg Asn Met Gly Glu Glu Pro Asn Tyr Gln 290 295 300Glu Glu Trp Val Met His Lys Lys Glu Val Val Leu Thr Val Pro Thr305 310 315 320Glu Gly Leu Glu Val Thr Trp Gly Asn Asn Glu Pro Tyr Lys Tyr Trp 325 330 335Pro Gln Leu Ser Thr Asn Gly Thr Ala His Gly His Pro His Glu Ile 340 345 350Ile Leu Tyr Tyr Tyr Glu Leu Tyr Pro Thr Met Thr 355 36020364PRTChikungunya virus 20Asp Asn Phe Asn Val Tyr Lys Ala Thr Arg Pro Tyr Leu Ala His Cys1 5 10 15Pro Asp Cys Gly Glu Gly His Ser Cys His Ser Pro Val Ala Leu Glu 20 25 30Arg Ile Arg Asn Glu Ala Thr Asp Gly Thr Leu Lys Ile Gln Val Ser 35 40 45Leu Gln Ile Gly Ile Lys Thr Asp Asp Ser His Asp Trp Thr Lys Leu 50 55 60Arg Tyr Met Asp Asn His Met Pro Ala Asp Ala Glu Arg Ala Gly Leu65 70 75 80Phe Val Arg Thr Ser Ala Pro Cys Thr Ile Thr Gly Thr Met Gly His 85 90 95Phe Ile Leu Ala Arg Cys Pro Lys Gly Glu Thr Leu Thr Val Gly Phe 100 105 110Thr Asp Ser Arg Lys Ile Ser His Ser Cys Thr His Pro Phe His His 115 120 125Asp Pro Pro Val Ile Gly Arg Glu Lys Phe His Ser Arg Pro Gln His 130 135 140Gly Lys Glu Leu Pro Cys Ser Thr Tyr Val Gln Ser Thr Ala Ala Thr145 150 155 160Thr Glu Glu Ile Glu Val His Met Pro Pro Asp Thr Pro Asp Arg Thr 165 170 175Leu Met Ser Gln Gln Ser Gly Asn Val Lys Ile Thr Val Asn Gly Gln 180 185 190Thr Val Arg Tyr Lys Cys Asn Cys Gly Gly Ser Asn Glu Gly Leu Thr 195 200 205Thr Thr Asp Lys Val Ile Asn Asn Cys Lys Val Asp Gln Cys His Ala 210 215 220Ala Val Thr Asn His Lys Lys Trp Gln Tyr Asn Ser Pro Leu Val Pro225 230 235 240Arg Asn Ala Glu Leu Gly Asp Arg Lys Gly Lys Ile His Ile Pro Phe 245 250 255Pro Leu Ala Asn Val Thr Cys Arg Val Pro Lys Ala Arg Asn Pro Thr 260 265 270Val Thr Tyr Gly Lys Asn Gln Val Ile Met Leu Leu Tyr Pro Asp His 275 280 285Pro Thr Leu Leu Ser Tyr Arg Asn Met Gly Glu Glu Pro Asn Tyr Gln 290 295 300Glu Glu Trp Val Met His Lys Lys Glu Val Val Leu Thr Val Pro Thr305 310 315 320Glu Gly Leu Glu Val Thr Trp Gly Asn Asn Glu Pro Tyr Lys Tyr Trp 325 330 335Pro Gln Leu Ser Thr Asn Gly Thr Ala His Gly His Pro His Glu Ile 340 345 350Ile Leu Tyr Tyr Tyr Glu Leu Tyr Pro Thr Met Thr 355 36021364PRTChikungunya virus 21Asp Asn Phe Asn Val Tyr Lys Ala Thr Arg Pro Tyr Leu Ala His Cys1 5 10 15Pro Asp Cys Gly Glu Gly His Ser Cys His Ser Pro Val Ala Leu Glu 20 25 30Arg Ile Arg Asn Glu Ala Thr Asp Gly Thr Leu Lys Ile Gln Val Ser 35 40 45Leu Gln Ile Gly Ile Lys Thr Asp Asp Ser His Asp Trp Thr Lys Leu 50 55 60Arg Tyr Met Asp Asn His Met Pro Ala Asp Ala Glu Arg Ala Gly Leu65 70 75 80Phe Val Arg Thr Ser Ala Pro Cys Thr Ile Thr Gly Thr Met Gly His 85 90 95Phe Ile Leu Ala Arg Cys Pro Lys Gly Glu Thr Leu Thr Val Gly Phe 100 105 110Thr Asp Ser Arg Lys Ile Ser His Ser Cys Thr His Pro Phe His His 115 120 125Asp Pro Pro Val Ile Gly Arg Glu Lys Phe His Ser Arg Pro Gln His 130 135 140Gly Lys Glu Leu Pro Cys Ser Thr Tyr Val Gln Ser Thr Ala Ala Thr145 150 155 160Thr Glu Glu Ile Glu Val His Met Pro Pro Asp Thr Pro Asp Arg Thr 165 170 175Leu Met Ser Gln Gln Ser Gly Asn Val Lys Ile Thr Val Asn Gly Gln 180 185 190Thr Val Arg Tyr Lys Cys Asn Cys Gly Gly Ser Asn Glu Gly Leu Thr 195 200 205Thr Thr Asp Lys Val Ile Asn Asn Cys Lys Val Asp Gln Cys His Ala 210 215 220Ala Val Thr Asn His Lys Lys Trp Gln Tyr Asn Ser Pro Leu Val Pro225 230 235 240Arg Asn Ala Glu Leu Gly Asp Arg Lys Gly Lys Ile His Ile Pro Phe 245 250 255Pro Leu Ala Asn Val Thr Cys Arg Val Pro Lys Ala Arg Asn Pro Thr 260 265 270Val Thr Tyr Gly Lys Asn Gln Val Ile Met Leu Leu Tyr Pro Asp His 275 280 285Pro Thr Leu Leu Ser Tyr Arg Asn Met Gly Glu Glu Pro Asn Tyr Gln 290 295 300Glu Glu Trp Val Met His Lys Lys Glu Val Val Leu Thr Val Pro Thr305 310 315 320Glu Gly Leu Glu Val Thr Trp Gly Asn Asn Glu Pro Tyr Lys Tyr Trp 325 330 335Pro Gln Leu Ser Thr Asn Gly Thr Ala His Gly His Pro His Glu Ile 340 345 350Ile Leu Tyr Tyr Tyr Glu Leu Tyr Pro Thr Met Thr 355 36022364PRTChikungunya virus 22Asp Asn Phe Asn Val Tyr Lys Ala Thr Arg Pro Tyr Leu Ala His Cys1 5 10 15Pro Asp Cys Gly Glu Gly His Ser Cys His Ser Pro Val Ala Leu Glu 20 25 30Arg Ile Arg Asn Glu Ala Thr Asp Gly Thr Leu Lys Ile Gln Val Ser 35 40 45Leu Gln Ile Gly Ile Lys Thr Asp Asp Ser His Asp Trp Thr Lys Leu 50 55 60Arg Tyr Met Asp Asn His Met Pro Ala Asp Ala Glu Arg Ala Gly Leu65 70 75 80Phe Val Arg Thr Ser Ala Pro Cys Thr Ile Thr Gly Thr Met Gly His 85 90 95Phe Ile Leu Ala Arg Cys Pro Lys Gly Glu Thr Leu Thr Val Gly Phe 100 105 110Thr Asp Ser Arg Lys Ile Ser His Ser Cys Thr His Pro Phe His His 115 120 125Asp Pro Pro Val Ile Gly Arg Glu Lys Phe His Ser Arg Pro Gln His 130 135 140Gly Lys Glu Ile Pro Cys Ser Thr Tyr Val Gln Ser Thr Ala Ala Thr145 150 155 160Thr Glu Glu Ile Glu Val His Met Pro Pro Asp Thr Pro Asp Arg Thr 165 170 175Leu Met Ser Gln Gln Ser Gly Asn Val Lys Ile Thr Val Asn Gly Gln 180 185 190Thr Val Arg Tyr Lys Cys Asn Cys Gly Gly Ser Asn Glu Gly Leu Thr 195 200 205Thr Thr Asp Lys Val Ile Asn Asn Cys Lys Val Asp Gln Cys His Ala 210 215 220Ala Val Thr Asn His Lys Lys Trp Gln Tyr Asn Ser Pro Leu Val Pro225 230 235 240Arg Asn Ala Glu Leu Gly Asp Arg Lys Gly Lys Ile His Ile Pro Phe 245 250 255Pro Leu Ala Asn Val Thr Cys Arg Val Pro Lys Ala Arg Asn Pro Thr 260 265 270Val Thr Tyr Gly Lys Asn Gln Val Ile Met Leu Leu Tyr Pro Asp His 275 280 285Pro Thr Leu Leu Ser Tyr Arg Asn Met Gly Glu Glu Pro Asn Tyr Gln 290 295 300Glu Glu Trp Val Met His Lys Lys Glu Val Val Leu Thr Val Pro Thr305 310 315 320Glu Gly Leu Glu Val Thr Trp Gly Asn Asn Glu Pro Tyr Lys Tyr Trp 325 330 335Pro Gln Leu Ser Thr Asn Gly Thr Ala His Gly His Pro His Glu Ile 340 345 350Ile Leu Tyr Tyr Tyr Glu Leu Tyr Pro Thr Met Thr 355 360231248PRTChikungunya virus 23Met Glu Phe Ile Pro Thr Gln Thr Phe Tyr Asn Arg Arg Tyr Gln Pro1 5 10 15Arg Pro Trp Thr Pro Arg Pro Thr Ile Gln Val Ile Arg Pro Arg Pro 20 25

30Arg Pro Gln Arg Gln Ala Gly Gln Leu Ala Gln Leu Ile Ser Ala Val 35 40 45Asn Lys Leu Thr Met Arg Ala Val Pro Gln Gln Lys Pro Arg Arg Asn 50 55 60Arg Lys Asn Lys Lys Gln Lys Gln Lys Gln Gln Ala Pro Gln Asn Asn65 70 75 80Thr Asn Gln Lys Lys Gln Pro Pro Lys Lys Lys Pro Ala Gln Lys Lys 85 90 95Lys Lys Pro Gly Arg Arg Glu Arg Met Cys Met Lys Ile Glu Asn Asp 100 105 110Cys Ile Phe Glu Val Lys His Glu Gly Lys Val Thr Gly Tyr Ala Cys 115 120 125Leu Val Gly Asp Lys Val Met Lys Pro Ala His Val Lys Gly Thr Ile 130 135 140Asp Asn Ala Asp Leu Ala Lys Leu Ala Phe Lys Arg Ser Ser Lys Tyr145 150 155 160Asp Leu Glu Cys Ala Gln Ile Pro Val His Met Lys Ser Asp Ala Ser 165 170 175Lys Phe Thr His Glu Lys Pro Glu Gly Tyr Tyr Asn Trp His His Gly 180 185 190Ala Val Gln Tyr Ser Gly Gly Arg Phe Thr Ile Pro Thr Gly Ala Gly 195 200 205Lys Pro Gly Asp Ser Gly Arg Pro Ile Phe Asp Asn Lys Gly Arg Val 210 215 220Val Ala Ile Val Leu Gly Gly Ala Asn Glu Gly Ala Arg Thr Ala Leu225 230 235 240Ser Val Val Thr Trp Asn Lys Asp Ile Val Thr Lys Ile Thr Pro Glu 245 250 255Gly Ala Glu Glu Trp Ser Leu Ala Ile Pro Val Met Cys Leu Leu Ala 260 265 270Asn Thr Thr Phe Pro Cys Ser Gln Pro Pro Cys Ile Pro Cys Cys Tyr 275 280 285Glu Lys Glu Pro Glu Glu Thr Leu Arg Met Leu Glu Asp Asn Val Met 290 295 300Arg Pro Gly Tyr Tyr Gln Leu Leu Gln Ala Ser Leu Thr Cys Ser Pro305 310 315 320His Arg Gln Arg Arg Ser Thr Lys Asp Asn Phe Asn Val Tyr Lys Ala 325 330 335Thr Arg Pro Tyr Leu Ala His Cys Pro Asp Cys Gly Glu Gly His Ser 340 345 350Cys His Ser Pro Val Ala Leu Glu Arg Ile Arg Asn Glu Ala Thr Asp 355 360 365Gly Thr Leu Lys Ile Gln Val Ser Leu Gln Ile Gly Ile Gly Thr Asp 370 375 380Asp Ser His Asp Trp Thr Lys Leu Arg Tyr Met Asp Asn His Ile Pro385 390 395 400Ala Asp Ala Gly Arg Ala Gly Leu Phe Val Arg Thr Ser Ala Pro Cys 405 410 415Thr Ile Thr Gly Thr Met Gly His Phe Ile Leu Ala Arg Cys Pro Lys 420 425 430Gly Glu Thr Leu Thr Val Gly Phe Thr Asp Ser Arg Lys Ile Ser His 435 440 445Ser Cys Thr His Pro Phe His His Asp Pro Pro Val Ile Gly Arg Glu 450 455 460Lys Phe His Ser Arg Pro Gln His Gly Lys Glu Leu Pro Cys Ser Thr465 470 475 480Tyr Val Gln Ser Asn Ala Ala Thr Ala Glu Glu Ile Glu Val His Met 485 490 495Pro Pro Asp Thr Pro Asp Arg Thr Leu Leu Ser Gln Gln Ser Gly Asn 500 505 510Val Lys Ile Thr Val Asn Gly Arg Thr Val Arg Tyr Lys Cys Asn Cys 515 520 525Gly Gly Ser Asn Glu Gly Leu Ile Thr Thr Asp Lys Val Ile Asn Asn 530 535 540Cys Lys Val Asp Gln Cys His Ala Ala Val Thr Asn His Lys Lys Trp545 550 555 560Gln Tyr Asn Ser Pro Leu Val Pro Arg Asn Ala Glu Leu Gly Asp Arg 565 570 575Lys Gly Lys Ile His Ile Pro Phe Pro Leu Ala Asn Val Thr Cys Met 580 585 590Val Pro Lys Ala Arg Asn Pro Thr Val Thr Tyr Gly Lys Asn Gln Val 595 600 605Ile Met Leu Leu Tyr Pro Asp His Pro Thr Leu Leu Ser Tyr Arg Ser 610 615 620Met Gly Glu Glu Pro Asn Tyr Gln Glu Glu Trp Val Thr His Lys Lys625 630 635 640Glu Val Val Leu Thr Val Pro Thr Glu Gly Leu Glu Val Thr Trp Gly 645 650 655Asn Asn Glu Pro Tyr Lys Tyr Trp Pro Gln Leu Ser Ala Asn Gly Thr 660 665 670Ala His Gly His Pro His Glu Ile Ile Leu Tyr Tyr Tyr Glu Leu Tyr 675 680 685Pro Thr Met Thr Val Val Val Val Ser Val Ala Ser Phe Ile Leu Leu 690 695 700Ser Met Val Gly Met Ala Val Gly Met Cys Met Cys Ala Arg Arg Arg705 710 715 720Cys Ile Thr Pro Tyr Glu Leu Thr Pro Gly Ala Thr Val Pro Phe Leu 725 730 735Leu Ser Leu Ile Cys Cys Ile Arg Thr Ala Lys Ala Ala Thr Tyr Gln 740 745 750Glu Ala Ala Val Tyr Leu Trp Asn Glu Gln Gln Pro Leu Phe Trp Leu 755 760 765Gln Ala Leu Ile Pro Leu Ala Ala Leu Ile Val Leu Cys Asn Cys Leu 770 775 780Arg Leu Leu Pro Cys Cys Cys Lys Thr Leu Ala Phe Leu Ala Val Met785 790 795 800Ser Ile Gly Ala His Thr Val Ser Ala Tyr Glu His Val Thr Val Ile 805 810 815Pro Asn Thr Val Gly Val Pro Tyr Lys Thr Leu Val Asn Arg Pro Gly 820 825 830Tyr Ser Pro Met Val Leu Glu Met Glu Leu Leu Ser Val Thr Leu Glu 835 840 845Pro Thr Leu Ser Leu Asp Tyr Ile Thr Cys Glu Tyr Lys Thr Val Ile 850 855 860Pro Ser Pro Tyr Val Lys Cys Cys Gly Thr Ala Glu Cys Lys Asp Lys865 870 875 880Asn Leu Pro Asp Tyr Ser Cys Lys Val Phe Thr Gly Val Tyr Pro Phe 885 890 895Met Trp Gly Gly Ala Tyr Cys Phe Cys Asp Ala Glu Asn Thr Gln Leu 900 905 910Ser Glu Ala His Val Glu Lys Ser Glu Ser Cys Lys Thr Glu Phe Ala 915 920 925Ser Ala Tyr Arg Ala His Thr Ala Ser Ala Ser Ala Lys Leu Arg Val 930 935 940Leu Tyr Gln Gly Asn Asn Ile Thr Val Thr Ala Tyr Ala Asn Gly Asp945 950 955 960His Ala Val Thr Val Lys Asp Ala Lys Phe Ile Val Gly Pro Met Ser 965 970 975Ser Ala Trp Thr Pro Phe Asp Asn Lys Ile Val Val Tyr Lys Gly Asp 980 985 990Val Tyr Asn Met Asp Tyr Pro Pro Phe Gly Ala Gly Arg Pro Gly Gln 995 1000 1005Phe Gly Asp Ile Gln Ser Arg Thr Pro Glu Ser Lys Asp Val Tyr 1010 1015 1020Ala Asn Thr Gln Leu Val Leu Gln Arg Pro Ala Ala Gly Thr Val 1025 1030 1035His Val Pro Tyr Ser Gln Ala Pro Ser Gly Phe Lys Tyr Trp Leu 1040 1045 1050Lys Glu Arg Gly Ala Ser Leu Gln His Thr Ala Pro Phe Gly Cys 1055 1060 1065Gln Ile Ala Thr Asn Pro Val Arg Ala Met Asn Cys Ala Val Gly 1070 1075 1080Asn Met Pro Ile Ser Ile Asp Ile Pro Asp Ala Ala Phe Thr Arg 1085 1090 1095Val Val Asp Ala Pro Ser Leu Thr Asp Met Ser Cys Glu Val Pro 1100 1105 1110Ala Cys Thr His Ser Ser Asp Phe Gly Gly Val Ala Ile Ile Lys 1115 1120 1125Tyr Ala Val Ser Lys Lys Gly Lys Cys Ala Val His Ser Met Thr 1130 1135 1140Asn Ala Val Thr Ile Arg Glu Ala Glu Ile Glu Val Glu Gly Asn 1145 1150 1155Ser Gln Leu Gln Ile Ser Phe Ser Thr Ala Leu Ala Ser Ala Glu 1160 1165 1170Phe Arg Val Gln Val Cys Ser Thr Gln Val His Cys Ala Ala Glu 1175 1180 1185Cys His Pro Pro Lys Asp His Ile Val Asn Tyr Pro Ala Ser His 1190 1195 1200Thr Thr Leu Gly Val Gln Asp Ile Ser Ala Thr Ala Met Ser Trp 1205 1210 1215Val Gln Lys Ile Thr Gly Gly Val Gly Leu Val Val Ala Val Ala 1220 1225 1230Ala Leu Ile Leu Ile Val Val Leu Cys Val Ser Phe Ser Arg His 1235 1240 1245241248PRTChikungunya virus 24Met Glu Phe Ile Pro Thr Gln Thr Phe Tyr Asn Arg Arg Tyr Gln Pro1 5 10 15Arg Pro Trp Thr Pro Arg Pro Thr Ile Gln Val Ile Arg Pro Arg Pro 20 25 30Arg Pro Gln Arg Gln Ala Gly Gln Leu Ala Gln Leu Ile Ser Ala Val 35 40 45Asn Lys Leu Thr Met Arg Ala Val Pro Gln Gln Lys Pro Arg Arg Asn 50 55 60Arg Lys Asn Lys Lys Gln Lys Gln Lys Gln Gln Ala Pro Gln Asn Asn65 70 75 80Thr Asn Gln Lys Lys Gln Pro Pro Lys Lys Lys Pro Ala Gln Lys Lys 85 90 95Lys Lys Pro Gly Arg Arg Glu Arg Met Cys Met Lys Ile Glu Asn Asp 100 105 110Cys Ile Phe Glu Val Lys His Glu Gly Lys Val Thr Gly Tyr Ala Cys 115 120 125Leu Val Gly Asp Lys Val Met Lys Pro Ala His Val Lys Gly Thr Ile 130 135 140Asp Asn Ala Asp Leu Ala Lys Leu Ala Phe Lys Arg Ser Ser Lys Tyr145 150 155 160Asp Leu Glu Cys Ala Gln Ile Pro Val His Met Lys Ser Asp Ala Ser 165 170 175Lys Phe Thr His Glu Lys Pro Glu Gly Tyr Tyr Asn Trp His His Gly 180 185 190Ala Val Gln Tyr Ser Gly Gly Arg Phe Thr Ile Pro Thr Gly Ala Gly 195 200 205Lys Pro Gly Asp Ser Gly Arg Pro Ile Phe Asp Asn Lys Gly Arg Val 210 215 220Val Ala Ile Val Leu Gly Gly Ala Asn Glu Gly Ala Arg Thr Ala Leu225 230 235 240Ser Val Val Thr Trp Asn Lys Asp Ile Val Thr Lys Ile Thr Pro Glu 245 250 255Gly Ala Glu Glu Trp Ser Leu Ala Ile Pro Val Met Cys Leu Leu Ala 260 265 270Asn Thr Thr Phe Pro Cys Ser Gln Pro Pro Cys Thr Pro Cys Cys Tyr 275 280 285Glu Lys Glu Pro Glu Glu Thr Leu Arg Met Leu Glu Asp Asn Val Met 290 295 300Arg Pro Gly Tyr Tyr Gln Leu Leu Gln Ala Ser Leu Thr Cys Ser Pro305 310 315 320His Arg Gln Arg Arg Ser Thr Lys Asp Asn Phe Asn Val Tyr Lys Ala 325 330 335Thr Arg Pro Tyr Leu Ala His Cys Pro Asp Cys Gly Glu Gly His Ser 340 345 350Cys His Ser Pro Val Ala Leu Glu Arg Ile Arg Asn Glu Ala Thr Asp 355 360 365Gly Thr Leu Lys Ile Gln Val Ser Leu Gln Ile Gly Ile Lys Thr Asp 370 375 380Asp Ser His Asp Trp Thr Lys Leu Arg Tyr Met Asp Asn His Met Pro385 390 395 400Ala Asp Ala Glu Arg Ala Gly Leu Phe Val Arg Thr Ser Ala Pro Cys 405 410 415Thr Ile Thr Gly Thr Met Gly His Phe Ile Leu Ala Arg Cys Pro Lys 420 425 430Gly Glu Thr Leu Thr Val Gly Phe Thr Asp Ser Arg Lys Ile Ser His 435 440 445Ser Cys Thr His Pro Phe His His Asp Pro Pro Val Ile Gly Arg Glu 450 455 460Lys Phe His Ser Arg Pro Gln His Gly Lys Glu Leu Pro Cys Ser Thr465 470 475 480Tyr Val Gln Ser Thr Ala Ala Thr Thr Glu Glu Ile Glu Val His Met 485 490 495Pro Pro Asp Thr Pro Asp Arg Thr Leu Met Ser Gln Gln Ser Gly Asn 500 505 510Val Lys Ile Thr Val Asn Gly Gln Thr Val Arg Tyr Lys Cys Asn Cys 515 520 525Gly Gly Ser Asn Glu Gly Leu Thr Thr Thr Asp Lys Val Ile Asn Asn 530 535 540Cys Lys Val Asp Gln Cys His Ala Ala Val Thr Asn His Lys Lys Trp545 550 555 560Gln Tyr Asn Ser Pro Leu Val Pro Arg Asn Ala Glu Leu Gly Asp Arg 565 570 575Lys Gly Lys Ile His Ile Pro Phe Pro Leu Ala Asn Val Thr Cys Arg 580 585 590Val Pro Lys Ala Arg Asn Pro Thr Val Thr Tyr Gly Lys Asn Gln Val 595 600 605Ile Met Leu Leu Tyr Pro Asp His Pro Thr Leu Leu Ser Tyr Arg Asn 610 615 620Met Gly Glu Glu Pro Asn Tyr Gln Glu Glu Trp Val Met His Lys Lys625 630 635 640Glu Val Val Leu Thr Val Pro Thr Glu Gly Leu Glu Val Thr Trp Gly 645 650 655Asn Asn Glu Pro Tyr Lys Tyr Trp Pro Gln Leu Ser Thr Asn Gly Thr 660 665 670Ala His Gly His Pro His Glu Ile Ile Leu Tyr Tyr Tyr Glu Leu Tyr 675 680 685Pro Thr Met Thr Val Val Val Val Ser Val Ala Thr Phe Ile Leu Leu 690 695 700Ser Met Val Gly Met Ala Ala Gly Met Cys Met Cys Ala Arg Arg Arg705 710 715 720Cys Ile Thr Pro Tyr Glu Leu Thr Pro Gly Ala Thr Val Pro Phe Leu 725 730 735Leu Ser Leu Ile Cys Cys Ile Arg Thr Ala Lys Ala Ala Thr Tyr Gln 740 745 750Glu Ala Ala Ile Tyr Leu Trp Asn Glu Gln Gln Pro Leu Phe Trp Leu 755 760 765Gln Ala Leu Ile Pro Leu Ala Ala Leu Ile Val Leu Cys Asn Cys Leu 770 775 780Arg Leu Leu Pro Cys Cys Cys Lys Thr Leu Ala Phe Leu Ala Val Met785 790 795 800Ser Val Gly Ala His Thr Val Ser Ala Tyr Glu His Val Thr Val Ile 805 810 815Pro Asn Thr Val Gly Val Pro Tyr Lys Thr Leu Val Asn Arg Pro Gly 820 825 830Tyr Ser Pro Met Val Leu Glu Met Glu Leu Leu Ser Val Thr Leu Glu 835 840 845Pro Thr Leu Ser Leu Asp Tyr Ile Thr Cys Glu Tyr Lys Thr Val Ile 850 855 860Pro Ser Pro Tyr Val Lys Cys Cys Gly Thr Ala Glu Cys Lys Asp Lys865 870 875 880Asn Leu Pro Asp Tyr Ser Cys Lys Val Phe Thr Gly Val Tyr Pro Phe 885 890 895Met Trp Gly Gly Ala Tyr Cys Phe Cys Asp Ala Glu Asn Thr Gln Leu 900 905 910Ser Glu Ala His Val Glu Lys Ser Glu Ser Cys Lys Thr Glu Phe Ala 915 920 925Ser Ala Tyr Arg Ala His Thr Ala Ser Ala Ser Ala Lys Leu Arg Val 930 935 940Leu Tyr Gln Gly Asn Asn Ile Thr Val Thr Ala Tyr Ala Asn Gly Asp945 950 955 960His Ala Val Thr Val Lys Asp Ala Lys Phe Ile Val Gly Pro Met Ser 965 970 975Ser Ala Trp Thr Pro Phe Asp Asn Lys Ile Val Val Tyr Lys Gly Asp 980 985 990Val Tyr Asn Met Asp Tyr Pro Pro Phe Gly Ala Gly Arg Pro Gly Gln 995 1000 1005Phe Gly Asp Ile Gln Ser Arg Thr Pro Glu Ser Lys Asp Val Tyr 1010 1015 1020Ala Asn Thr Gln Leu Val Leu Gln Arg Pro Ala Ala Gly Thr Val 1025 1030 1035His Val Pro Tyr Ser Gln Ala Pro Ser Gly Phe Lys Tyr Trp Leu 1040 1045 1050Lys Glu Arg Gly Ala Ser Leu Gln His Thr Ala Pro Phe Gly Cys 1055 1060 1065Gln Ile Ala Thr Asn Pro Val Arg Ala Val Asn Cys Ala Val Gly 1070 1075 1080Asn Met Pro Ile Ser Ile Asp Ile Pro Glu Ala Ala Phe Thr Arg 1085 1090 1095Val Val Asp Ala Pro Ser Leu Thr Asp Met Ser Cys Glu Val Pro 1100 1105 1110Ala Cys Thr His Ser Ser Asp Phe Gly Gly Val Ala Ile Ile Lys 1115 1120 1125Tyr Ala Ala Ser Lys Lys Gly Lys Cys Ala Val His Ser Met Thr 1130 1135 1140Asn Ala Val Thr Ile Arg Glu Ala Glu Ile Glu Val Glu Gly Asn 1145 1150 1155Ser Gln Leu Gln Ile Ser Phe Ser Thr Ala Leu Ala Ser Ala Glu 1160 1165 1170Phe Arg Val Gln Val Cys Ser Thr Gln Val His Cys Ala Ala Glu 1175 1180 1185Cys His Pro Pro Lys Asp His Ile Val Asn Tyr Pro Ala Ser His 1190 1195 1200Thr Thr Leu Gly Val Gln Asp Ile Ser Ala Thr Ala Met Ser Trp 1205 1210 1215Val Gln Lys Ile Thr Gly Gly Val Gly Leu Val Val Ala Val Ala 1220 1225 1230Ala Leu Ile Leu Ile Val Val Leu Cys Val Ser Phe Ser Arg His 1235

1240 1245251248PRTChikungunya virus 25Met Glu Phe Ile Pro Thr Gln Thr Phe Tyr Asn Arg Arg Tyr Gln Pro1 5 10 15Arg Pro Trp Thr Pro Arg Pro Thr Ile Gln Val Ile Arg Pro Arg Pro 20 25 30Arg Pro Gln Arg Gln Ala Gly Gln Leu Ala Gln Leu Ile Ser Ala Val 35 40 45Asn Lys Leu Thr Met Arg Ala Val Pro Gln Gln Lys Pro Arg Arg Asn 50 55 60Arg Lys Asn Lys Lys Gln Lys Gln Lys Gln Gln Ala Pro Gln Asn Asn65 70 75 80Thr Asn Gln Lys Lys Gln Pro Pro Lys Lys Lys Pro Ala Gln Lys Lys 85 90 95Lys Lys Pro Gly Arg Arg Glu Arg Met Cys Met Lys Ile Glu Asn Asp 100 105 110Cys Ile Phe Glu Val Lys His Glu Gly Lys Val Thr Gly Tyr Ala Cys 115 120 125Leu Val Gly Asp Lys Val Met Lys Pro Ala His Val Lys Gly Thr Ile 130 135 140Asp Asn Ala Asp Leu Ala Lys Leu Ala Phe Lys Arg Ser Ser Lys Tyr145 150 155 160Asp Leu Glu Cys Ala Gln Ile Pro Val His Met Lys Ser Asp Ala Ser 165 170 175Lys Phe Thr His Glu Lys Pro Glu Gly Tyr Tyr Asn Trp His His Gly 180 185 190Ala Val Gln Tyr Ser Gly Gly Arg Phe Thr Ile Pro Thr Gly Ala Gly 195 200 205Lys Pro Gly Asp Ser Gly Arg Pro Ile Phe Asp Asn Lys Gly Arg Val 210 215 220Val Ala Ile Val Leu Gly Gly Ala Asn Glu Gly Ala Arg Thr Ala Leu225 230 235 240Ser Val Val Thr Trp Asn Lys Asp Ile Val Thr Lys Ile Thr Pro Glu 245 250 255Gly Ala Glu Glu Trp Ser Leu Ala Ile Pro Val Met Cys Leu Leu Ala 260 265 270Asn Thr Thr Phe Pro Cys Ser Gln Pro Pro Cys Thr Pro Cys Cys Tyr 275 280 285Glu Lys Glu Pro Glu Glu Thr Leu Arg Met Leu Glu Asp Asn Val Met 290 295 300Arg Pro Gly Tyr Tyr Gln Leu Leu Gln Ala Ser Leu Thr Cys Ser Pro305 310 315 320His Arg Gln Arg Arg Ser Thr Lys Asp Asn Phe Asn Val Tyr Lys Ala 325 330 335Thr Arg Pro Tyr Leu Ala His Cys Pro Asp Cys Gly Glu Gly His Ser 340 345 350Cys His Ser Pro Val Ala Leu Glu Arg Ile Arg Asn Glu Ala Thr Asp 355 360 365Gly Thr Leu Lys Ile Gln Val Ser Leu Gln Ile Gly Ile Lys Thr Asp 370 375 380Asp Ser His Asp Trp Thr Lys Leu Arg Tyr Met Asp Asn His Met Pro385 390 395 400Ala Asp Ala Glu Arg Ala Gly Leu Phe Val Arg Thr Ser Ala Pro Cys 405 410 415Thr Ile Thr Gly Thr Met Gly His Phe Ile Leu Ala Arg Cys Pro Lys 420 425 430Gly Glu Thr Leu Thr Val Gly Phe Thr Asp Ser Arg Lys Ile Ser His 435 440 445Ser Cys Thr His Pro Phe His His Asp Pro Pro Val Ile Gly Arg Glu 450 455 460Lys Phe His Ser Arg Pro Arg His Gly Lys Glu Leu Pro Cys Ser Thr465 470 475 480Tyr Val Gln Ser Thr Ala Ala Thr Thr Glu Glu Ile Glu Val His Met 485 490 495Pro Pro Asp Thr Pro Asp Arg Thr Leu Met Ser Gln Gln Ser Gly Asn 500 505 510Val Lys Ile Thr Val Asn Gly Gln Thr Val Arg Tyr Lys Cys Asn Cys 515 520 525Gly Gly Ser Asn Glu Gly Leu Thr Thr Thr Asp Lys Val Ile Asn Asn 530 535 540Cys Lys Val Asp Gln Cys His Ala Ala Val Thr Asn His Lys Lys Trp545 550 555 560Gln Tyr Asn Ser Pro Leu Val Pro Arg Asn Ala Glu Leu Gly Asp Arg 565 570 575Lys Gly Lys Ile His Ile Pro Phe Pro Leu Ala Asn Val Thr Cys Arg 580 585 590Val Pro Lys Ala Arg Asn Pro Thr Val Thr Tyr Gly Lys Asn Gln Val 595 600 605Ile Met Leu Leu Tyr Pro Asp His Pro Thr Leu Leu Ser Tyr Arg Asn 610 615 620Met Gly Glu Glu Pro Asn Tyr Gln Glu Glu Trp Val Met His Lys Lys625 630 635 640Glu Val Val Leu Thr Val Pro Thr Glu Gly Leu Glu Val Thr Trp Gly 645 650 655Asn Asn Glu Pro Tyr Lys Tyr Trp Pro Gln Leu Ser Thr Asn Gly Thr 660 665 670Ala His Gly His Pro His Glu Ile Ile Leu Tyr Tyr Tyr Glu Leu Tyr 675 680 685Pro Thr Met Thr Val Val Val Val Ser Val Ala Thr Phe Ile Leu Leu 690 695 700Ser Met Val Gly Met Ala Ala Gly Met Cys Met Cys Ala Arg Arg Arg705 710 715 720Cys Ile Thr Pro Tyr Glu Leu Thr Pro Gly Ala Thr Val Pro Phe Leu 725 730 735Leu Ser Leu Ile Cys Cys Ile Arg Thr Ala Lys Ala Ala Thr Tyr Gln 740 745 750Glu Ala Ala Ile Tyr Leu Trp Asn Glu Gln Gln Pro Leu Phe Trp Leu 755 760 765Gln Ala Leu Ile Pro Leu Ala Ala Leu Ile Val Leu Cys Asn Cys Leu 770 775 780Arg Leu Leu Pro Cys Cys Cys Lys Thr Leu Ala Phe Leu Ala Val Met785 790 795 800Ser Val Gly Ala His Thr Val Ser Ala Tyr Glu His Val Thr Val Ile 805 810 815Pro Asn Thr Val Gly Val Pro Tyr Lys Thr Leu Val Asn Arg Pro Gly 820 825 830Tyr Ser Pro Met Val Leu Glu Met Glu Leu Leu Ser Val Thr Leu Glu 835 840 845Pro Thr Leu Ser Leu Asp Tyr Ile Thr Cys Glu Tyr Lys Thr Val Ile 850 855 860Pro Ser Pro Tyr Val Lys Cys Cys Gly Thr Ala Glu Cys Lys Asp Lys865 870 875 880Asn Leu Pro Asp Tyr Ser Cys Lys Val Phe Thr Gly Val Tyr Pro Phe 885 890 895Met Trp Gly Gly Ala Tyr Cys Phe Cys Asp Ala Glu Asn Thr Gln Leu 900 905 910Ser Glu Ala His Val Glu Lys Ser Glu Ser Cys Lys Thr Glu Phe Ala 915 920 925Ser Ala Tyr Arg Ala His Thr Ala Ser Ala Ser Ala Lys Leu Arg Val 930 935 940Leu Tyr Gln Gly Asn Asn Ile Thr Val Thr Ala Tyr Ala Asn Gly Asp945 950 955 960His Ala Val Thr Val Lys Asp Ala Lys Phe Ile Val Gly Pro Met Ser 965 970 975Ser Ala Trp Thr Pro Phe Asp Asn Lys Ile Val Val Tyr Lys Gly Asp 980 985 990Val Tyr Asn Met Asp Tyr Pro Pro Phe Gly Ala Gly Arg Pro Gly Gln 995 1000 1005Phe Gly Asp Ile Gln Ser Arg Thr Pro Glu Ser Lys Asp Val Tyr 1010 1015 1020Ala Asn Thr Gln Leu Val Leu Gln Arg Pro Ala Ala Gly Thr Val 1025 1030 1035His Val Pro Tyr Ser Gln Ala Pro Ser Gly Phe Lys Tyr Trp Leu 1040 1045 1050Lys Glu Arg Gly Ala Ser Leu Gln His Thr Ala Pro Phe Gly Cys 1055 1060 1065Gln Ile Ala Thr Asn Pro Val Arg Ala Val Asn Cys Ala Val Gly 1070 1075 1080Asn Met Pro Ile Ser Ile Asp Ile Pro Glu Ala Ala Phe Thr Arg 1085 1090 1095Val Val Asp Ala Pro Ser Leu Thr Asp Met Ser Cys Glu Val Pro 1100 1105 1110Ala Cys Thr His Ser Ser Asp Phe Gly Gly Val Ala Ile Ile Lys 1115 1120 1125Tyr Ala Ala Ser Lys Lys Gly Lys Cys Ala Val His Ser Met Thr 1130 1135 1140Asn Ala Val Thr Ile Arg Glu Ala Glu Ile Glu Val Glu Gly Asn 1145 1150 1155Ser Gln Leu Gln Ile Ser Phe Ser Thr Ala Leu Ala Ser Ala Glu 1160 1165 1170Phe Arg Val Gln Val Cys Ser Thr Gln Val His Cys Ala Ala Glu 1175 1180 1185Cys His Pro Pro Lys Asp His Ile Val Asn Tyr Pro Ala Ser His 1190 1195 1200Thr Thr Leu Gly Val Gln Asp Ile Ser Ala Thr Ala Met Ser Trp 1205 1210 1215Val Gln Lys Ile Thr Gly Gly Val Gly Leu Val Val Ala Val Ala 1220 1225 1230Ala Leu Ile Leu Ile Val Val Leu Cys Val Ser Phe Ser Arg His 1235 1240 1245261248PRTChikungunya virus 26Met Glu Phe Ile Pro Thr Gln Thr Phe Tyr Asn Arg Arg Tyr Gln Pro1 5 10 15Arg Pro Trp Thr Pro Arg Pro Thr Ile Gln Val Ile Arg Pro Arg Pro 20 25 30Arg Pro Gln Arg Gln Ala Gly Gln Leu Ala Gln Leu Ile Ser Ala Val 35 40 45Asn Lys Leu Thr Met Arg Ala Val Pro Gln Gln Lys Pro Arg Arg Asn 50 55 60Arg Lys Asn Lys Lys Gln Lys Gln Lys Gln Gln Ala Pro Gln Asn Asn65 70 75 80Thr Asn Gln Lys Lys Gln Pro Pro Lys Lys Lys Pro Ala Gln Lys Lys 85 90 95Lys Lys Pro Gly Arg Arg Glu Arg Met Cys Met Lys Ile Glu Asn Asp 100 105 110Cys Ile Phe Glu Val Lys His Glu Gly Lys Val Thr Gly Tyr Ala Cys 115 120 125Leu Val Gly Asp Lys Val Met Lys Pro Ala His Val Lys Gly Thr Ile 130 135 140Asp Asn Ala Asp Leu Ala Lys Leu Ala Phe Lys Arg Ser Ser Lys Tyr145 150 155 160Asp Leu Glu Cys Ala Gln Ile Pro Val His Met Lys Ser Asp Ala Ser 165 170 175Lys Phe Thr His Glu Lys Pro Glu Gly Tyr Tyr Asn Trp His His Gly 180 185 190Ala Val Gln Tyr Ser Gly Gly Arg Phe Thr Ile Pro Thr Gly Ala Gly 195 200 205Lys Pro Gly Asp Ser Gly Arg Pro Ile Phe Asp Asn Lys Gly Arg Val 210 215 220Val Ala Ile Val Leu Gly Gly Ala Asn Glu Gly Ala Arg Thr Ala Leu225 230 235 240Ser Val Val Thr Trp Asn Lys Asp Ile Val Thr Lys Ile Thr Pro Glu 245 250 255Gly Ala Glu Glu Trp Ser Leu Ala Ile Pro Val Met Cys Leu Leu Ala 260 265 270Asn Thr Thr Phe Pro Cys Ser Gln Pro Pro Cys Thr Pro Cys Cys Tyr 275 280 285Glu Lys Glu Pro Glu Glu Thr Leu Arg Met Leu Glu Asp Asn Val Met 290 295 300Arg Pro Gly Tyr Tyr Gln Leu Leu Gln Ala Ser Leu Thr Cys Ser Pro305 310 315 320His Arg Gln Arg Arg Ser Thr Lys Asp Asn Phe Asn Val Tyr Lys Ala 325 330 335Thr Arg Pro Tyr Leu Ala His Cys Pro Asp Cys Gly Glu Gly His Ser 340 345 350Cys His Ser Pro Val Ala Leu Glu Arg Ile Arg Asn Glu Ala Thr Asp 355 360 365Gly Thr Leu Lys Ile Gln Val Ser Leu Gln Ile Gly Ile Lys Thr Asp 370 375 380Asp Ser His Asp Trp Thr Lys Leu Arg Tyr Met Asp Asn His Met Pro385 390 395 400Ala Asp Ala Glu Arg Ala Gly Leu Phe Val Arg Thr Ser Ala Pro Cys 405 410 415Thr Ile Thr Gly Thr Met Gly His Phe Ile Leu Ala Arg Cys Pro Lys 420 425 430Gly Glu Thr Leu Thr Val Gly Phe Thr Asp Ser Arg Lys Ile Ser His 435 440 445Ser Cys Thr His Pro Phe His His Asp Pro Pro Val Ile Gly Arg Glu 450 455 460Lys Phe His Ser Arg Pro Gln His Gly Lys Glu Leu Pro Cys Ser Thr465 470 475 480Tyr Val Gln Ser Thr Ala Ala Thr Thr Glu Glu Ile Glu Val His Met 485 490 495Pro Pro Asp Thr Pro Asp Arg Thr Leu Met Ser Gln Gln Ser Gly Asn 500 505 510Val Lys Ile Thr Val Asn Gly Gln Thr Val Arg Tyr Lys Cys Asn Cys 515 520 525Gly Gly Ser Asn Glu Gly Leu Thr Thr Thr Asp Lys Val Ile Asn Asn 530 535 540Cys Lys Val Asp Gln Cys His Ala Ala Val Thr Asn His Lys Lys Trp545 550 555 560Gln Tyr Asn Ser Pro Leu Val Pro Arg Asn Ala Glu Leu Gly Asp Arg 565 570 575Lys Gly Lys Ile His Ile Pro Phe Pro Leu Ala Asn Val Thr Cys Arg 580 585 590Val Pro Lys Ala Arg Asn Pro Thr Val Thr Tyr Gly Lys Asn Gln Val 595 600 605Ile Met Leu Leu Tyr Pro Asp His Pro Thr Leu Leu Ser Tyr Arg Asn 610 615 620Met Gly Glu Glu Pro Asn Tyr Gln Glu Glu Trp Val Met His Lys Lys625 630 635 640Glu Val Val Leu Thr Val Pro Thr Glu Gly Leu Glu Val Thr Trp Gly 645 650 655Asn Asn Glu Pro Tyr Lys Tyr Trp Pro Gln Leu Ser Thr Asn Gly Thr 660 665 670Ala His Gly His Pro His Glu Ile Ile Leu Tyr Tyr Tyr Glu Leu Tyr 675 680 685Pro Thr Met Thr Val Val Val Val Ser Val Ala Thr Phe Ile Leu Leu 690 695 700Ser Met Val Gly Met Ala Ala Gly Met Cys Met Cys Ala Arg Arg Arg705 710 715 720Cys Ile Thr Pro Tyr Glu Leu Thr Pro Gly Ala Thr Val Pro Phe Leu 725 730 735Leu Ser Leu Ile Cys Cys Ile Arg Thr Ala Lys Ala Ala Thr Tyr Gln 740 745 750Glu Ala Ala Ile Tyr Leu Trp Asn Glu Gln Gln Pro Leu Phe Trp Leu 755 760 765Gln Ala Leu Ile Pro Leu Ala Ala Leu Ile Val Leu Cys Asn Cys Leu 770 775 780Arg Leu Leu Pro Cys Cys Cys Lys Thr Leu Ala Phe Leu Ala Val Met785 790 795 800Ser Val Gly Ala His Thr Val Ser Ala Tyr Glu His Val Thr Val Ile 805 810 815Pro Asn Thr Val Gly Val Pro Tyr Lys Thr Leu Val Asn Arg Pro Gly 820 825 830Tyr Ser Pro Met Val Leu Glu Met Glu Leu Leu Ser Val Thr Leu Glu 835 840 845Pro Thr Leu Ser Leu Asp Tyr Ile Thr Cys Glu Tyr Lys Thr Val Ile 850 855 860Pro Ser Pro Tyr Val Lys Cys Cys Gly Thr Ala Glu Cys Lys Asp Lys865 870 875 880Asn Leu Pro Asp Tyr Ser Cys Lys Val Phe Thr Gly Val Tyr Pro Phe 885 890 895Met Trp Gly Gly Ala Tyr Cys Phe Cys Asp Ala Glu Asn Thr Gln Leu 900 905 910Ser Glu Ala His Val Glu Lys Ser Glu Ser Cys Lys Thr Glu Phe Ala 915 920 925Ser Ala Tyr Arg Ala His Thr Ala Ser Ala Ser Ala Lys Leu Arg Val 930 935 940Leu Tyr Gln Gly Asn Asn Ile Thr Val Thr Ala Tyr Ala Asn Gly Asp945 950 955 960His Ala Val Thr Val Lys Asp Ala Lys Phe Ile Val Gly Pro Met Ser 965 970 975Ser Ala Trp Thr Pro Phe Asp Asn Lys Ile Val Val Tyr Lys Gly Asp 980 985 990Val Tyr Asn Met Asp Tyr Pro Pro Phe Gly Ala Gly Arg Pro Gly Gln 995 1000 1005Phe Gly Asp Ile Gln Ser Arg Thr Pro Glu Ser Lys Asp Val Tyr 1010 1015 1020Ala Asn Thr Gln Leu Val Leu Gln Arg Pro Ala Ala Gly Thr Val 1025 1030 1035His Val Pro Tyr Ser Gln Ala Pro Ser Gly Phe Lys Tyr Trp Leu 1040 1045 1050Lys Glu Arg Gly Ala Ser Leu Gln His Thr Ala Pro Phe Gly Cys 1055 1060 1065Gln Ile Ala Thr Asn Pro Val Arg Ala Val Asn Cys Ala Val Gly 1070 1075 1080Asn Met Pro Ile Ser Ile Asp Ile Pro Glu Ala Ala Phe Thr Arg 1085 1090 1095Val Val Asp Ala Pro Ser Leu Thr Asp Met Ser Cys Glu Val Pro 1100 1105 1110Ala Cys Thr His Ser Ser Asp Phe Gly Gly Val Ala Ile Ile Lys 1115 1120 1125Tyr Ala Ala Ser Lys Lys Gly Lys Cys Ala Val His Ser Met Thr 1130 1135 1140Asn Ala Val Thr Ile Arg Glu Ala Glu Ile Glu Val Glu Gly Asn 1145 1150 1155Ser Gln Leu Gln Ile Ser Phe Ser Thr Ala Leu Ala Ser Ala Glu 1160 1165 1170Phe Arg Val Gln Val Cys Ser Thr Gln Val His Cys Ala Ala Glu 1175 1180 1185Cys His Pro Pro Lys Asp His Ile Val Asn Tyr Pro Ala Ser His 1190 1195 1200Thr Thr

Leu Gly Val Gln Asp Ile Ser Ala Thr Ala Met Ser Trp 1205 1210 1215Val Gln Lys Ile Thr Gly Gly Val Gly Leu Val Val Ala Val Ala 1220 1225 1230Ala Leu Ile Leu Ile Val Val Leu Cys Val Ser Phe Ser Arg His 1235 1240 1245271248PRTChikungunya virus 27Met Glu Phe Ile Pro Thr Gln Thr Phe Tyr Asn Arg Arg Tyr Gln Pro1 5 10 15Arg Pro Trp Thr Pro Arg Pro Thr Ile Gln Val Ile Arg Pro Arg Pro 20 25 30Arg Pro Gln Arg Gln Ala Gly Gln Leu Ala Gln Leu Ile Ser Ala Val 35 40 45Asn Lys Leu Thr Met Arg Ala Val Pro Gln Gln Lys Pro Arg Arg Asn 50 55 60Arg Lys Asn Lys Lys Gln Lys Gln Lys Gln Gln Ala Pro Gln Asn Asn65 70 75 80Thr Asn Gln Lys Lys Gln Pro Pro Lys Lys Lys Pro Ala Gln Lys Lys 85 90 95Lys Lys Pro Gly Arg Arg Glu Arg Met Cys Met Lys Ile Glu Asn Asp 100 105 110Cys Ile Phe Glu Val Lys His Glu Gly Lys Val Thr Gly Tyr Ala Cys 115 120 125Leu Val Gly Asp Lys Val Met Lys Pro Ala His Val Lys Gly Thr Ile 130 135 140Asp Asn Ala Asp Leu Ala Lys Leu Ala Phe Lys Arg Ser Ser Lys Tyr145 150 155 160Asp Leu Glu Cys Ala Gln Ile Pro Val His Met Lys Ser Asp Ala Ser 165 170 175Lys Phe Thr His Glu Lys Pro Glu Gly Tyr Tyr Asn Trp His His Gly 180 185 190Ala Val Gln Tyr Ser Gly Gly Arg Phe Thr Ile Pro Thr Gly Ala Gly 195 200 205Lys Pro Gly Asp Ser Gly Arg Pro Ile Phe Asp Asn Lys Gly Arg Val 210 215 220Val Ala Ile Val Leu Gly Gly Ala Asn Glu Gly Ala Arg Thr Ala Leu225 230 235 240Ser Val Val Thr Trp Asn Lys Asp Ile Val Thr Lys Ile Thr Pro Glu 245 250 255Gly Ala Glu Glu Trp Ser Leu Ala Ile Pro Val Met Cys Leu Leu Ala 260 265 270Asn Thr Thr Phe Pro Cys Ser Gln Pro Pro Cys Thr Pro Cys Cys Tyr 275 280 285Glu Lys Glu Pro Glu Glu Thr Leu Arg Met Leu Glu Asp Asn Val Met 290 295 300Arg Pro Gly Tyr Tyr Gln Leu Leu Gln Ala Ser Leu Thr Cys Ser Pro305 310 315 320His Arg Gln Arg Arg Ser Thr Lys Asp Asn Phe Asn Val Tyr Lys Ala 325 330 335Thr Arg Pro Tyr Leu Ala His Cys Pro Asp Cys Gly Glu Gly His Ser 340 345 350Cys His Ser Pro Val Ala Leu Glu Arg Ile Arg Asn Glu Ala Thr Asp 355 360 365Gly Thr Leu Lys Ile Gln Val Ser Leu Gln Ile Gly Ile Lys Thr Asp 370 375 380Asp Ser His Asp Trp Thr Lys Leu Arg Tyr Met Asp Asn His Met Pro385 390 395 400Ala Asp Ala Glu Arg Ala Gly Leu Phe Val Arg Thr Ser Ala Pro Cys 405 410 415Thr Ile Thr Gly Thr Met Gly His Phe Ile Leu Ala Arg Cys Pro Lys 420 425 430Gly Glu Thr Leu Thr Val Gly Phe Thr Asp Ser Arg Lys Ile Ser His 435 440 445Ser Cys Thr His Pro Phe His His Asp Pro Pro Val Ile Gly Arg Glu 450 455 460Lys Phe His Ser Arg Pro Gln His Gly Lys Glu Leu Pro Cys Ser Thr465 470 475 480Tyr Val Gln Ser Thr Ala Ala Thr Thr Glu Glu Ile Glu Val His Met 485 490 495Pro Pro Asp Thr Pro Asp Arg Thr Leu Met Ser Gln Gln Ser Gly Asn 500 505 510Val Lys Ile Thr Val Asn Gly Gln Thr Val Arg Tyr Lys Cys Asn Cys 515 520 525Gly Gly Ser Asn Glu Gly Leu Thr Thr Thr Asp Lys Val Ile Asn Asn 530 535 540Cys Lys Val Asp Gln Cys His Ala Ala Val Thr Asn His Lys Lys Trp545 550 555 560Gln Tyr Asn Ser Pro Leu Val Pro Arg Asn Ala Glu Leu Gly Asp Arg 565 570 575Lys Gly Lys Ile His Ile Pro Phe Pro Leu Ala Asn Val Thr Cys Arg 580 585 590Val Pro Lys Ala Arg Asn Pro Thr Val Thr Tyr Gly Lys Asn Gln Val 595 600 605Ile Met Leu Leu Tyr Pro Asp His Pro Thr Leu Leu Ser Tyr Arg Asn 610 615 620Met Gly Glu Glu Pro Asn Tyr Gln Glu Glu Trp Val Met His Lys Lys625 630 635 640Glu Val Val Leu Thr Val Pro Thr Glu Gly Leu Glu Val Thr Trp Gly 645 650 655Asn Asn Glu Pro Tyr Lys Tyr Trp Pro Gln Leu Ser Thr Asn Gly Thr 660 665 670Ala His Gly His Pro His Glu Ile Ile Leu Tyr Tyr Tyr Glu Leu Tyr 675 680 685Pro Thr Met Thr Val Val Val Val Ser Val Ala Thr Phe Ile Leu Leu 690 695 700Ser Met Val Gly Met Ala Ala Gly Met Cys Met Cys Ala Arg Arg Arg705 710 715 720Cys Ile Thr Pro Tyr Glu Leu Thr Pro Gly Ala Thr Val Pro Phe Leu 725 730 735Leu Ser Leu Ile Cys Cys Ile Arg Thr Ala Lys Ala Ala Thr Tyr Gln 740 745 750Glu Ala Ala Ile Tyr Leu Trp Asn Glu Gln Gln Pro Leu Phe Trp Leu 755 760 765Gln Ala Leu Ile Pro Leu Ala Ala Leu Ile Val Leu Cys Asn Cys Leu 770 775 780Arg Leu Leu Pro Cys Cys Cys Lys Thr Leu Ala Phe Leu Ala Val Met785 790 795 800Ser Val Gly Ala His Thr Val Ser Ala Tyr Glu His Val Thr Val Ile 805 810 815Pro Asn Thr Val Gly Val Pro Tyr Lys Thr Leu Val Asn Arg Pro Gly 820 825 830Tyr Ser Pro Met Val Leu Glu Met Glu Leu Leu Ser Val Thr Leu Glu 835 840 845Pro Thr Leu Ser Leu Asp Tyr Ile Thr Cys Glu Tyr Lys Thr Val Ile 850 855 860Pro Ser Pro Tyr Val Lys Cys Cys Gly Thr Ala Glu Cys Lys Asp Lys865 870 875 880Asn Leu Pro Asp Tyr Ser Cys Lys Val Phe Thr Gly Val Tyr Pro Phe 885 890 895Met Trp Gly Gly Ala Tyr Cys Phe Cys Asp Ala Glu Asn Thr Gln Leu 900 905 910Ser Glu Ala His Val Glu Lys Ser Glu Ser Cys Lys Thr Glu Phe Ala 915 920 925Ser Ala Tyr Arg Ala His Thr Ala Ser Ala Ser Ala Lys Leu Arg Val 930 935 940Leu Tyr Gln Gly Asn Asn Ile Thr Val Thr Ala Tyr Ala Asn Gly Asp945 950 955 960His Ala Val Thr Val Lys Asp Ala Lys Phe Ile Val Gly Pro Met Ser 965 970 975Ser Ala Trp Thr Pro Phe Asp Asn Lys Ile Val Val Tyr Lys Gly Asp 980 985 990Val Tyr Asn Met Asp Tyr Pro Pro Phe Gly Ala Gly Arg Pro Gly Gln 995 1000 1005Phe Gly Asp Ile Gln Ser Arg Thr Pro Glu Ser Lys Asp Val Tyr 1010 1015 1020Ala Asn Thr Gln Leu Val Leu Gln Arg Pro Ala Val Gly Thr Val 1025 1030 1035His Val Pro Tyr Ser Gln Ala Pro Ser Gly Phe Lys Tyr Trp Leu 1040 1045 1050Lys Glu Arg Gly Ala Ser Leu Gln His Thr Ala Pro Phe Gly Cys 1055 1060 1065Gln Ile Ala Thr Asn Pro Val Arg Ala Val Asn Cys Ala Val Gly 1070 1075 1080Asn Met Pro Ile Ser Ile Asp Ile Pro Glu Ala Ala Phe Thr Arg 1085 1090 1095Val Val Asp Ala Pro Ser Leu Thr Asp Met Ser Cys Glu Val Pro 1100 1105 1110Ala Cys Thr His Ser Ser Asp Phe Gly Gly Val Ala Ile Ile Lys 1115 1120 1125Tyr Ala Ala Ser Lys Lys Gly Lys Cys Ala Val His Ser Met Thr 1130 1135 1140Asn Ala Val Thr Ile Arg Glu Ala Glu Ile Glu Val Glu Gly Asn 1145 1150 1155Ser Gln Leu Gln Ile Ser Phe Ser Thr Ala Leu Ala Ser Ala Glu 1160 1165 1170Phe Arg Val Gln Val Cys Ser Thr Gln Val His Cys Ala Ala Glu 1175 1180 1185Cys His Pro Pro Lys Asp His Ile Val Asn Tyr Pro Ala Ser His 1190 1195 1200Thr Thr Leu Gly Val Gln Asp Ile Ser Ala Thr Ala Met Ser Trp 1205 1210 1215Val Gln Lys Ile Thr Gly Gly Val Gly Leu Val Val Ala Val Ala 1220 1225 1230Ala Leu Ile Leu Ile Val Val Leu Cys Val Ser Phe Ser Arg His 1235 1240 1245281248PRTChikungunya virus 28Met Glu Phe Ile Pro Thr Gln Thr Phe Tyr Asn Arg Arg Tyr Gln Pro1 5 10 15Arg Pro Trp Thr Pro Arg Pro Thr Ile Gln Val Ile Arg Pro Arg Pro 20 25 30Arg Pro Gln Arg Gln Ala Gly Gln Leu Ala Gln Leu Ile Ser Ala Val 35 40 45Asn Lys Leu Thr Met Arg Ala Val Pro Gln Gln Lys Pro Arg Arg Asn 50 55 60Arg Lys Asn Lys Lys Gln Lys Gln Lys Gln Gln Ala Pro Gln Asn Asn65 70 75 80Thr Asn Gln Lys Lys Gln Pro Pro Lys Lys Lys Pro Ala Gln Lys Lys 85 90 95Lys Lys Pro Gly Arg Arg Glu Arg Met Cys Met Lys Ile Glu Asn Asp 100 105 110Cys Ile Phe Glu Val Lys His Glu Gly Lys Val Thr Gly Tyr Ala Cys 115 120 125Leu Val Gly Asp Lys Val Met Lys Pro Ala His Val Lys Gly Thr Ile 130 135 140Asp Asn Ala Asp Leu Ala Lys Leu Ala Phe Lys Arg Ser Ser Lys Tyr145 150 155 160Asp Leu Glu Cys Ala Gln Ile Pro Val His Met Lys Ser Asp Ala Ser 165 170 175Lys Phe Thr His Glu Lys Pro Glu Gly Tyr Tyr Asn Trp His His Gly 180 185 190Ala Val Gln Tyr Ser Gly Gly Arg Phe Thr Ile Pro Thr Gly Ala Gly 195 200 205Lys Pro Gly Asp Ser Gly Arg Pro Ile Phe Asp Asn Lys Gly Arg Val 210 215 220Val Ala Ile Val Leu Gly Gly Ala Asn Glu Gly Ala Arg Thr Ala Leu225 230 235 240Ser Val Val Thr Trp Asn Lys Asp Ile Val Thr Lys Ile Thr Pro Glu 245 250 255Gly Ala Glu Glu Trp Ser Leu Ala Ile Pro Val Met Cys Leu Leu Ala 260 265 270Asn Thr Thr Phe Pro Cys Ser Gln Pro Pro Cys Thr Pro Cys Cys Tyr 275 280 285Glu Lys Glu Pro Glu Glu Thr Leu Arg Met Leu Glu Asp Asn Val Met 290 295 300Arg Pro Gly Tyr Tyr Gln Leu Leu Gln Ala Ser Leu Thr Cys Ser Pro305 310 315 320His Arg Gln Arg Arg Ser Thr Lys Asp Asn Phe Asn Val Tyr Lys Ala 325 330 335Thr Arg Pro Tyr Leu Ala His Cys Pro Asp Cys Gly Glu Gly His Ser 340 345 350Cys His Ser Pro Val Ala Leu Glu Arg Ile Arg Asn Glu Ala Thr Asp 355 360 365Gly Thr Leu Lys Ile Gln Val Ser Leu Gln Ile Gly Ile Lys Thr Asp 370 375 380Asp Ser His Asp Trp Thr Lys Leu Arg Tyr Met Asp Asn His Met Pro385 390 395 400Ala Asp Ala Glu Arg Ala Gly Leu Phe Val Arg Thr Ser Ala Pro Cys 405 410 415Thr Ile Thr Gly Thr Met Gly His Phe Ile Leu Ala Arg Cys Pro Lys 420 425 430Gly Glu Thr Leu Thr Val Gly Phe Thr Asp Ser Arg Lys Ile Ser His 435 440 445Ser Cys Thr His Pro Phe His His Asp Pro Pro Val Ile Gly Arg Glu 450 455 460Lys Phe His Ser Arg Pro Gln His Gly Lys Glu Leu Pro Cys Ser Thr465 470 475 480Tyr Val Gln Ser Thr Ala Ala Thr Thr Glu Glu Ile Glu Val His Met 485 490 495Pro Pro Asp Thr Pro Asp Arg Thr Leu Met Ser Gln Gln Ser Gly Asn 500 505 510Val Lys Ile Thr Val Asn Gly Gln Thr Val Arg Tyr Lys Cys Asn Cys 515 520 525Gly Gly Ser Asn Glu Gly Leu Thr Thr Thr Asp Lys Val Ile Asn Asn 530 535 540Cys Lys Val Asp Gln Cys His Ala Ala Val Thr Asn His Lys Lys Trp545 550 555 560Gln Tyr Asn Ser Pro Leu Val Pro Arg Asn Ala Glu Leu Gly Asp Arg 565 570 575Lys Gly Lys Ile His Ile Pro Phe Pro Leu Ala Asn Val Thr Cys Arg 580 585 590Val Pro Lys Ala Arg Asn Pro Thr Val Thr Tyr Gly Lys Asn Gln Val 595 600 605Ile Met Leu Leu Tyr Pro Asp His Pro Thr Leu Leu Ser Tyr Arg Asn 610 615 620Met Gly Glu Glu Pro Asn Tyr Gln Glu Glu Trp Val Met His Lys Lys625 630 635 640Glu Val Val Leu Thr Val Pro Thr Glu Gly Leu Glu Val Thr Trp Gly 645 650 655Asn Asn Glu Pro Tyr Lys Tyr Trp Pro Gln Leu Ser Thr Asn Gly Thr 660 665 670Ala His Gly His Pro His Glu Ile Ile Leu Tyr Tyr Tyr Glu Leu Tyr 675 680 685Pro Thr Met Thr Val Val Val Val Ser Val Ala Thr Phe Ile Leu Leu 690 695 700Ser Met Val Gly Met Ala Ala Gly Met Cys Met Cys Ala Arg Arg Arg705 710 715 720Cys Ile Thr Pro Tyr Glu Leu Thr Pro Gly Ala Thr Val Pro Phe Leu 725 730 735Leu Ser Leu Ile Cys Cys Ile Arg Thr Ala Lys Ala Ala Thr Tyr Gln 740 745 750Glu Ala Ala Ile Tyr Leu Trp Asn Glu Gln Gln Pro Leu Phe Trp Leu 755 760 765Gln Ala Leu Ile Pro Leu Ala Ala Leu Ile Val Leu Cys Asn Cys Leu 770 775 780Arg Leu Leu Pro Cys Cys Cys Lys Thr Leu Ala Phe Leu Ala Val Met785 790 795 800Ser Val Gly Ala His Thr Val Ser Ala Tyr Glu His Val Thr Val Ile 805 810 815Pro Asn Thr Val Gly Val Pro Tyr Lys Thr Leu Val Asn Arg Pro Gly 820 825 830Tyr Ser Pro Met Val Leu Glu Met Glu Leu Leu Ser Val Thr Leu Glu 835 840 845Pro Thr Leu Ser Leu Asp Tyr Ile Thr Cys Glu Tyr Lys Thr Val Ile 850 855 860Pro Ser Pro Tyr Val Lys Cys Cys Gly Thr Ala Glu Cys Lys Asp Lys865 870 875 880Asn Leu Pro Asp Tyr Ser Cys Lys Val Phe Thr Gly Val Tyr Pro Phe 885 890 895Met Trp Gly Gly Ala Tyr Cys Phe Cys Asp Ala Glu Asn Thr Gln Leu 900 905 910Ser Glu Ala His Val Glu Lys Ser Glu Ser Cys Lys Thr Glu Phe Ala 915 920 925Ser Ala Tyr Arg Ala His Thr Ala Ser Ala Ser Ala Lys Leu Arg Val 930 935 940Leu Tyr Gln Gly Asn Asn Ile Thr Val Thr Ala Tyr Ala Asn Gly Asp945 950 955 960His Ala Val Thr Val Lys Asp Ala Lys Phe Ile Val Gly Pro Met Ser 965 970 975Ser Ala Trp Thr Pro Phe Asp Asn Lys Ile Val Val Tyr Lys Gly Asp 980 985 990Val Tyr Asn Met Asp Tyr Pro Pro Phe Gly Ala Gly Arg Pro Gly Gln 995 1000 1005Phe Gly Asp Ile Gln Ser Arg Thr Pro Glu Ser Lys Asp Val Tyr 1010 1015 1020Ala Asn Thr Gln Leu Val Leu Gln Arg Pro Ala Val Gly Thr Val 1025 1030 1035His Val Pro Tyr Ser Gln Ala Pro Ser Gly Phe Lys Tyr Trp Leu 1040 1045 1050Lys Glu Arg Gly Ala Ser Leu Gln His Thr Ala Pro Phe Gly Cys 1055 1060 1065Gln Ile Ala Thr Asn Pro Val Arg Ala Val Asn Cys Ala Val Gly 1070 1075 1080Asn Met Pro Ile Ser Ile Asp Ile Pro Glu Ala Ala Phe Thr Arg 1085 1090 1095Val Val Asp Ala Pro Ser Leu Thr Asp Met Ser Cys Glu Val Pro 1100 1105 1110Ala Cys Thr His Ser Ser Asp Phe Gly Gly Val Ala Ile Ile Lys 1115 1120 1125Tyr Ala Ala Ser Lys Lys Gly Lys Cys Ala Val His Ser Met Thr 1130 1135 1140Asn Ala Val Thr Ile Arg Glu Ala Glu Ile Glu Val Glu Gly Asn 1145 1150 1155Ser Gln Leu Gln Ile Ser Phe Ser Thr Ala Leu Ala Ser

Ala Glu 1160 1165 1170Phe Arg Val Gln Val Cys Ser Thr Gln Val His Cys Ala Ala Glu 1175 1180 1185Cys His Pro Pro Lys Asp His Ile Val Asn Tyr Pro Ala Ser His 1190 1195 1200Thr Thr Leu Gly Val Gln Asp Ile Ser Ala Thr Ala Met Ser Trp 1205 1210 1215Val Gln Lys Ile Thr Gly Gly Val Gly Leu Val Val Ala Val Ala 1220 1225 1230Ala Leu Ile Leu Ile Val Val Leu Cys Val Ser Phe Ser Arg His 1235 1240 1245291248PRTChikungunya virus 29Met Glu Phe Ile Pro Thr Gln Thr Phe Tyr Asn Arg Arg Tyr Gln Pro1 5 10 15Arg Pro Trp Thr Pro Arg Pro Thr Ile Gln Val Ile Arg Pro Arg Pro 20 25 30Arg Pro Gln Arg Gln Ala Gly Gln Leu Ala Gln Leu Ile Ser Ala Val 35 40 45Asn Lys Leu Thr Met Arg Ala Val Pro Gln Gln Lys Pro Arg Arg Asn 50 55 60Arg Lys Asn Lys Lys Gln Lys Gln Lys Gln Gln Ala Pro Gln Asn Asn65 70 75 80Thr Asn Gln Lys Lys Gln Pro Pro Lys Lys Lys Pro Ala Gln Lys Lys 85 90 95Lys Lys Pro Gly Arg Arg Glu Arg Met Cys Met Lys Ile Glu Asn Asp 100 105 110Cys Ile Phe Glu Val Lys His Glu Gly Lys Val Thr Gly Tyr Ala Cys 115 120 125Leu Val Gly Asp Lys Val Met Lys Pro Ala His Val Lys Gly Thr Ile 130 135 140Asp Asn Ala Asp Leu Ala Lys Leu Ala Phe Lys Arg Ser Ser Lys Tyr145 150 155 160Asp Leu Glu Cys Ala Gln Ile Pro Val His Met Lys Ser Asp Ala Ser 165 170 175Lys Phe Thr His Glu Lys Pro Glu Gly Tyr Tyr Asn Trp His His Gly 180 185 190Ala Val Gln Tyr Ser Gly Gly Arg Phe Thr Ile Pro Thr Gly Ala Gly 195 200 205Lys Pro Gly Asp Ser Gly Arg Pro Ile Phe Asp Asn Lys Gly Arg Val 210 215 220Val Ala Ile Val Leu Gly Gly Ala Asn Glu Gly Ala Arg Thr Ala Leu225 230 235 240Ser Val Val Thr Trp Asn Lys Asp Ile Val Thr Lys Ile Thr Pro Glu 245 250 255Gly Ala Glu Glu Trp Ser Leu Ala Ile Pro Val Met Cys Leu Leu Ala 260 265 270Asn Thr Thr Phe Pro Cys Ser Gln Pro Pro Cys Thr Pro Cys Cys Tyr 275 280 285Glu Lys Glu Pro Glu Glu Thr Leu Arg Met Leu Glu Asp Asn Val Met 290 295 300Arg Pro Gly Tyr Tyr Gln Leu Leu Gln Ala Ser Leu Thr Cys Ser Pro305 310 315 320His Arg Gln Arg Arg Ser Thr Lys Asp Asn Phe Asn Val Tyr Lys Ala 325 330 335Thr Arg Pro Tyr Leu Ala His Cys Pro Asp Cys Gly Glu Gly His Ser 340 345 350Cys His Ser Pro Val Ala Leu Glu Arg Ile Arg Asn Glu Ala Thr Asp 355 360 365Gly Thr Leu Lys Ile Gln Val Ser Leu Gln Ile Gly Ile Lys Thr Asp 370 375 380Asp Ser His Asp Trp Thr Lys Leu Arg Tyr Met Asp Asn His Met Pro385 390 395 400Ala Asp Ala Glu Arg Ala Gly Leu Phe Val Arg Thr Ser Ala Pro Cys 405 410 415Thr Ile Thr Gly Thr Met Gly His Phe Ile Leu Ala Arg Cys Pro Lys 420 425 430Gly Glu Thr Leu Thr Val Gly Phe Thr Asp Ser Arg Lys Ile Ser His 435 440 445Ser Cys Thr His Pro Phe His His Asp Pro Pro Val Ile Gly Arg Glu 450 455 460Lys Phe His Ser Arg Pro Gln His Gly Lys Glu Leu Pro Cys Ser Thr465 470 475 480Tyr Val Gln Ser Thr Ala Ala Thr Thr Glu Glu Ile Glu Val His Met 485 490 495Pro Pro Asp Thr Pro Asp Arg Thr Leu Met Ser Gln Gln Ser Gly Asn 500 505 510Val Lys Ile Thr Val Asn Gly Gln Thr Val Arg Tyr Lys Cys Asn Cys 515 520 525Gly Gly Ser Asn Glu Gly Leu Thr Thr Thr Asp Lys Val Ile Asn Asn 530 535 540Cys Lys Val Asp Gln Cys His Ala Ala Val Thr Asn His Lys Lys Trp545 550 555 560Gln Tyr Asn Ser Pro Leu Val Pro Arg Asn Ala Glu Leu Gly Asp Arg 565 570 575Lys Gly Lys Ile His Ile Pro Phe Pro Leu Ala Asn Val Thr Cys Arg 580 585 590Val Pro Lys Ala Arg Asn Pro Thr Val Thr Tyr Gly Lys Asn Gln Val 595 600 605Ile Met Leu Leu Tyr Pro Asp His Pro Thr Leu Leu Ser Tyr Arg Asn 610 615 620Met Gly Glu Glu Pro Asn Tyr Gln Glu Glu Trp Val Met His Lys Lys625 630 635 640Glu Val Val Leu Thr Val Pro Thr Glu Gly Leu Glu Val Thr Trp Gly 645 650 655Asn Asn Glu Pro Tyr Lys Tyr Trp Pro Gln Leu Ser Thr Asn Gly Thr 660 665 670Ala His Gly His Pro His Glu Ile Ile Leu Tyr Tyr Tyr Glu Leu Tyr 675 680 685Pro Thr Met Thr Val Val Val Val Ser Val Ala Thr Phe Ile Leu Leu 690 695 700Ser Met Val Gly Met Ala Ala Gly Met Cys Met Cys Ala Arg Arg Arg705 710 715 720Cys Ile Thr Pro Tyr Glu Leu Thr Pro Gly Ala Thr Val Pro Phe Leu 725 730 735Leu Ser Leu Ile Cys Cys Ile Arg Thr Ala Lys Ala Ala Thr Tyr Gln 740 745 750Glu Ala Ala Ile Tyr Leu Trp Asn Glu Gln Gln Pro Leu Phe Trp Leu 755 760 765Gln Ala Leu Ile Pro Leu Ala Ala Leu Ile Val Leu Cys Asn Cys Leu 770 775 780Arg Leu Leu Pro Cys Cys Cys Lys Thr Leu Ala Phe Leu Ala Val Met785 790 795 800Ser Val Gly Ala His Thr Val Ser Ala Tyr Glu His Val Thr Val Ile 805 810 815Pro Asn Thr Val Gly Val Pro Tyr Lys Thr Leu Val Asn Arg Pro Gly 820 825 830Tyr Ser Pro Met Val Leu Glu Met Glu Leu Leu Ser Val Thr Leu Glu 835 840 845Pro Thr Leu Ser Leu Asp Tyr Ile Thr Cys Glu Tyr Lys Thr Val Ile 850 855 860Pro Ser Pro Tyr Val Lys Cys Cys Gly Thr Ala Glu Cys Lys Asp Lys865 870 875 880Asn Leu Pro Asp Tyr Ser Cys Lys Val Phe Thr Gly Val Tyr Pro Phe 885 890 895Met Trp Gly Gly Ala Tyr Cys Phe Cys Asp Ala Glu Asn Thr Gln Leu 900 905 910Ser Glu Ala His Val Glu Lys Ser Glu Ser Cys Lys Thr Glu Phe Ala 915 920 925Ser Ala Tyr Arg Ala His Thr Ala Ser Ala Ser Ala Lys Leu Arg Val 930 935 940Leu Tyr Gln Gly Asn Asn Ile Thr Val Thr Ala Tyr Ala Asn Gly Asp945 950 955 960His Ala Val Thr Val Lys Asp Ala Lys Phe Ile Val Gly Pro Met Ser 965 970 975Ser Ala Trp Thr Pro Phe Asp Asn Lys Ile Val Val Tyr Lys Gly Asp 980 985 990Val Tyr Asn Met Asp Tyr Pro Pro Phe Gly Ala Gly Arg Pro Gly Gln 995 1000 1005Phe Gly Asp Ile Gln Ser Arg Thr Pro Glu Ser Lys Asp Val Tyr 1010 1015 1020Ala Asn Thr Gln Leu Val Leu Gln Arg Pro Ala Val Gly Thr Val 1025 1030 1035His Val Pro Tyr Ser Gln Ala Pro Ser Gly Phe Lys Tyr Trp Leu 1040 1045 1050Lys Glu Arg Gly Ala Ser Leu Gln His Thr Ala Pro Phe Gly Cys 1055 1060 1065Gln Ile Ala Thr Asn Pro Val Arg Ala Val Asn Cys Ala Val Gly 1070 1075 1080Asn Met Pro Ile Ser Ile Asp Ile Pro Glu Ala Ala Phe Thr Arg 1085 1090 1095Val Val Asp Ala Pro Ser Leu Thr Asp Met Ser Cys Glu Val Pro 1100 1105 1110Ala Cys Thr His Ser Ser Asp Phe Gly Gly Val Ala Ile Ile Lys 1115 1120 1125Tyr Ala Ala Ser Lys Lys Gly Lys Cys Ala Val His Ser Met Thr 1130 1135 1140Asn Ala Val Thr Ile Arg Glu Ala Glu Ile Glu Val Glu Gly Asn 1145 1150 1155Ser Gln Leu Gln Ile Ser Phe Ser Thr Ala Leu Ala Ser Ala Glu 1160 1165 1170Phe Arg Val Gln Val Cys Ser Thr Gln Val His Cys Ala Ala Glu 1175 1180 1185Cys His Pro Pro Lys Asp His Ile Val Asn Tyr Pro Ala Ser His 1190 1195 1200Thr Thr Leu Gly Val Gln Asp Ile Ser Ala Thr Ala Met Ser Trp 1205 1210 1215Val Gln Lys Ile Thr Gly Gly Val Gly Leu Val Val Ala Val Ala 1220 1225 1230Ala Leu Ile Leu Ile Val Val Leu Cys Val Ser Phe Ser Arg His 1235 1240 1245302473PRTChikungunya virus 30Met Asp Pro Val Tyr Val Asp Ile Asp Ala Asp Ser Ala Phe Leu Lys1 5 10 15Ala Leu Gln Arg Ala Tyr Pro Met Phe Glu Val Glu Pro Arg Gln Val 20 25 30Thr Pro Asn Asp His Ala Asn Ala Arg Ala Phe Ser His Leu Ala Ile 35 40 45Lys Leu Ile Glu Gln Glu Ile Asp Pro Asp Ser Thr Ile Leu Asp Ile 50 55 60Gly Ser Ala Pro Ala Arg Arg Met Met Ser Asp Arg Lys Tyr His Cys65 70 75 80Val Cys Pro Met Arg Ser Ala Glu Asp Pro Glu Arg Leu Ala Asn Tyr 85 90 95Ala Arg Lys Leu Ala Ser Ala Ala Gly Lys Val Leu Asp Arg Asn Ile 100 105 110Ser Gly Lys Ile Gly Asp Leu Gln Ala Val Met Ala Val Pro Asp Thr 115 120 125Glu Thr Pro Thr Phe Cys Leu His Thr Asp Val Ser Cys Arg Gln Arg 130 135 140Ala Asp Val Ala Ile Tyr Gln Asp Val Tyr Ala Val His Ala Pro Thr145 150 155 160Ser Leu Tyr His Gln Ala Ile Lys Gly Val Arg Val Ala Tyr Trp Val 165 170 175Gly Phe Asp Thr Thr Pro Phe Met Tyr Asn Ala Met Ala Gly Ala Tyr 180 185 190Pro Ser Tyr Ser Thr Asn Trp Ala Asp Glu Gln Val Leu Lys Ala Lys 195 200 205Asn Ile Gly Leu Cys Ser Thr Asp Leu Thr Glu Gly Arg Arg Gly Lys 210 215 220Leu Ser Ile Met Arg Gly Lys Lys Leu Lys Pro Cys Asp Arg Val Leu225 230 235 240Phe Ser Val Gly Ser Thr Leu Tyr Pro Glu Ser Arg Lys Leu Leu Lys 245 250 255Ser Trp His Leu Pro Ser Val Phe His Leu Lys Gly Lys Leu Ser Phe 260 265 270Thr Cys Arg Cys Asp Thr Val Val Ser Cys Glu Gly Tyr Val Val Lys 275 280 285Arg Ile Thr Met Ser Pro Gly Leu Tyr Gly Lys Thr Thr Gly Tyr Ala 290 295 300Val Thr His His Ala Asp Gly Phe Leu Met Cys Lys Thr Thr Asp Thr305 310 315 320Val Asp Gly Glu Arg Val Ser Phe Ser Val Cys Thr Tyr Val Pro Ala 325 330 335Thr Ile Cys Asp Gln Met Thr Gly Ile Leu Ala Thr Glu Val Thr Pro 340 345 350Glu Asp Ala Gln Lys Leu Leu Val Gly Leu Asn Gln Arg Ile Val Val 355 360 365Asn Gly Arg Thr Gln Arg Asn Thr Asn Thr Met Lys Asn Tyr Leu Leu 370 375 380Pro Val Val Ala Gln Ala Phe Ser Lys Trp Ala Lys Glu Cys Arg Lys385 390 395 400Asp Met Glu Asp Glu Lys Leu Leu Gly Val Arg Glu Arg Thr Leu Thr 405 410 415Cys Cys Cys Leu Trp Ala Phe Lys Lys Gln Lys Thr His Thr Val Tyr 420 425 430Lys Arg Pro Asp Thr Gln Ser Ile Gln Lys Val Gln Ala Glu Phe Asp 435 440 445Ser Phe Val Val Pro Ser Leu Trp Ser Ser Gly Leu Ser Ile Pro Leu 450 455 460Arg Thr Arg Ile Lys Trp Leu Leu Ser Lys Val Pro Lys Thr Asp Leu465 470 475 480Ile Pro Tyr Ser Gly Asp Ala Arg Glu Ala Arg Asp Ala Glu Lys Glu 485 490 495Ala Glu Glu Glu Arg Glu Ala Glu Leu Thr Arg Glu Ala Leu Pro Pro 500 505 510Leu Gln Ala Ala Gln Glu Asp Val Gln Val Glu Ile Asp Val Glu Gln 515 520 525Leu Glu Asp Arg Ala Gly Ala Gly Ile Ile Glu Thr Pro Arg Gly Ala 530 535 540Ile Lys Val Thr Ala Gln Pro Thr Asp His Val Val Gly Glu Tyr Leu545 550 555 560Val Leu Ser Pro Gln Thr Val Leu Arg Ser Gln Lys Leu Ser Leu Ile 565 570 575His Ala Leu Ala Glu Gln Val Lys Thr Cys Thr His Asn Gly Arg Ala 580 585 590Gly Arg Tyr Ala Val Glu Ala Tyr Asp Gly Arg Val Leu Val Pro Ser 595 600 605Gly Tyr Ala Ile Ser Pro Glu Asp Phe Gln Ser Leu Ser Glu Ser Ala 610 615 620Thr Met Val Tyr Asn Glu Arg Glu Phe Val Asn Arg Lys Leu His His625 630 635 640Ile Ala Met His Gly Pro Ala Leu Asn Thr Asp Glu Glu Ser Tyr Glu 645 650 655Leu Val Arg Ala Glu Arg Thr Glu His Glu Tyr Val Tyr Asp Val Asp 660 665 670Gln Arg Arg Cys Cys Lys Lys Glu Glu Ala Ala Gly Leu Val Leu Val 675 680 685Gly Asp Leu Thr Asn Pro Pro Tyr His Glu Phe Ala Tyr Glu Gly Leu 690 695 700Lys Ile Arg Pro Ala Cys Pro Tyr Lys Ile Ala Val Ile Gly Val Phe705 710 715 720Gly Val Pro Gly Ser Gly Lys Ser Ala Ile Ile Lys Asn Leu Val Thr 725 730 735Arg Gln Asp Leu Val Thr Ser Gly Lys Lys Glu Asn Cys Gln Glu Ile 740 745 750Thr Thr Asp Val Met Arg Gln Arg Gly Leu Glu Ile Ser Ala Arg Thr 755 760 765Val Asp Ser Leu Leu Leu Asn Gly Cys Asn Arg Pro Val Asp Val Leu 770 775 780Tyr Val Asp Glu Ala Phe Ala Cys His Ser Gly Thr Leu Leu Ala Leu785 790 795 800Ile Ala Leu Val Arg Pro Arg Gln Lys Val Val Leu Cys Gly Asp Pro 805 810 815Lys Gln Cys Gly Phe Phe Asn Met Met Gln Met Lys Val Asn Tyr Asn 820 825 830His Asn Ile Cys Thr Gln Val Tyr His Lys Ser Ile Ser Arg Arg Cys 835 840 845Thr Leu Pro Val Thr Ala Ile Val Ser Ser Leu His Tyr Glu Gly Lys 850 855 860Met Arg Thr Thr Asn Glu Tyr Asn Lys Pro Ile Val Val Asp Thr Thr865 870 875 880Gly Ser Thr Lys Pro Asp Pro Gly Asp Leu Val Leu Thr Cys Phe Arg 885 890 895Gly Trp Val Lys Gln Leu Gln Ile Asp Tyr Arg Gly Tyr Glu Val Met 900 905 910Thr Ala Ala Ala Ser Gln Gly Leu Thr Arg Lys Gly Val Tyr Ala Val 915 920 925Arg Gln Lys Val Asn Glu Asn Pro Leu Tyr Ala Ser Thr Ser Glu His 930 935 940Val Asn Val Leu Leu Thr Arg Thr Glu Gly Lys Leu Val Trp Lys Thr945 950 955 960Leu Ser Gly Asp Pro Trp Ile Lys Thr Leu Gln Asn Pro Pro Lys Gly 965 970 975Asn Phe Lys Ala Thr Ile Lys Glu Trp Glu Val Glu His Ala Ser Ile 980 985 990Met Ala Gly Ile Cys Ser His Gln Met Thr Phe Asp Thr Phe Gln Asn 995 1000 1005Lys Ala Asn Val Cys Trp Ala Lys Ser Leu Val Pro Ile Leu Glu 1010 1015 1020Thr Ala Gly Ile Lys Leu Asn Asp Arg Gln Trp Ser Gln Ile Ile 1025 1030 1035Gln Ala Phe Lys Glu Asp Lys Ala Tyr Ser Pro Glu Val Ala Leu 1040 1045 1050Asn Glu Ile Cys Thr Arg Met Tyr Gly Val Asp Leu Asp Ser Gly 1055 1060 1065Leu Phe Ser Lys Pro Leu Val Ser Val Tyr Tyr Ala Asp Asn His 1070 1075 1080Trp Asp Asn Arg Pro Gly Gly Lys Met Phe Gly Phe Asn Pro Glu 1085 1090 1095Ala Ala Ser Ile Leu Glu Arg Lys Tyr Pro Phe Thr Lys Gly Lys 1100 1105 1110Trp Asn Ile Asn Lys Gln Ile Cys Val Thr Thr Arg Arg Ile Glu 1115 1120

1125Asp Phe Asn Pro Thr Thr Asn Ile Ile Pro Ala Asn Arg Arg Leu 1130 1135 1140Pro His Ser Leu Val Ala Glu His Arg Pro Val Lys Gly Glu Arg 1145 1150 1155Met Glu Trp Leu Val Asn Lys Ile Asn Gly His His Val Leu Leu 1160 1165 1170Val Ser Gly Tyr Asn Leu Ala Leu Pro Thr Lys Arg Val Thr Trp 1175 1180 1185Val Ala Pro Leu Gly Val Arg Gly Ala Asp Tyr Thr Tyr Asn Leu 1190 1195 1200Glu Leu Gly Leu Pro Ala Thr Leu Gly Arg Tyr Asp Leu Val Val 1205 1210 1215Ile Asn Ile His Thr Pro Phe Arg Ile His His Tyr Gln Gln Cys 1220 1225 1230Val Asp His Ala Met Lys Leu Gln Met Leu Gly Gly Asp Ser Leu 1235 1240 1245Arg Leu Leu Lys Pro Gly Gly Ser Leu Leu Ile Arg Ala Tyr Gly 1250 1255 1260Tyr Ala Asp Arg Thr Ser Glu Arg Val Ile Cys Val Leu Gly Arg 1265 1270 1275Lys Phe Arg Ser Ser Arg Ala Leu Lys Pro Pro Cys Val Thr Ser 1280 1285 1290Asn Thr Glu Met Phe Phe Leu Phe Ser Asn Phe Asp Asn Gly Arg 1295 1300 1305Arg Asn Phe Thr Thr His Val Met Asn Asn Gln Leu Asn Ala Ala 1310 1315 1320Phe Val Gly Gln Val Thr Arg Ala Gly Cys Ala Pro Ser Tyr Arg 1325 1330 1335Val Lys Arg Met Asp Ile Ala Lys Asn Asp Glu Glu Cys Val Val 1340 1345 1350Asn Ala Ala Asn Pro Arg Gly Leu Pro Gly Asp Gly Val Cys Lys 1355 1360 1365Ala Val Tyr Lys Lys Trp Pro Glu Ser Phe Lys Asn Ser Ala Thr 1370 1375 1380Pro Val Gly Thr Ala Lys Thr Val Met Cys Gly Thr Tyr Pro Val 1385 1390 1395Ile His Ala Val Gly Pro Asn Phe Ser Asn Tyr Ser Glu Ser Glu 1400 1405 1410Gly Asp Arg Glu Leu Ala Ala Ala Tyr Arg Glu Val Ala Lys Glu 1415 1420 1425Val Thr Arg Leu Gly Val Asn Ser Val Ala Ile Pro Leu Leu Ser 1430 1435 1440Thr Gly Val Tyr Ser Gly Gly Lys Asp Arg Leu Thr Gln Ser Leu 1445 1450 1455Asn His Leu Phe Thr Ala Met Asp Ser Thr Asp Ala Asp Val Val 1460 1465 1470Ile Tyr Cys Arg Asp Lys Glu Trp Glu Lys Lys Ile Ser Glu Ala 1475 1480 1485Ile Gln Met Arg Thr Gln Val Glu Leu Leu Asp Glu His Ile Ser 1490 1495 1500Ile Asp Cys Asp Ile Val Arg Val His Pro Asp Ser Ser Leu Ala 1505 1510 1515Gly Arg Lys Gly Tyr Ser Thr Thr Glu Gly Ala Leu Tyr Ser Tyr 1520 1525 1530Leu Glu Gly Thr Arg Phe His Gln Thr Ala Val Asp Met Ala Glu 1535 1540 1545Ile His Thr Met Trp Pro Lys Gln Thr Glu Ala Asn Glu Gln Val 1550 1555 1560Cys Leu Tyr Ala Leu Gly Glu Ser Ile Glu Ser Ile Arg Gln Lys 1565 1570 1575Cys Pro Val Asp Asp Ala Asp Ala Ser Ser Pro Pro Lys Thr Val 1580 1585 1590Pro Cys Leu Cys Arg Tyr Ala Met Thr Pro Glu Arg Val Thr Arg 1595 1600 1605Leu Arg Met Asn His Val Thr Ser Ile Ile Val Cys Ser Ser Phe 1610 1615 1620Pro Leu Pro Lys Tyr Lys Ile Glu Gly Val Gln Lys Val Lys Cys 1625 1630 1635Ser Lys Val Met Leu Phe Asp His Asn Val Pro Ser Arg Val Ser 1640 1645 1650Pro Arg Glu Tyr Arg Ser Ser Gln Glu Ser Ala Gln Glu Ala Ser 1655 1660 1665Thr Ile Thr Ser Leu Thr His Ser Gln Phe Asp Leu Ser Val Asp 1670 1675 1680Gly Glu Ile Leu Pro Val Pro Ser Asp Leu Asp Ala Asp Ala Pro 1685 1690 1695Ala Leu Glu Pro Ala Leu Asp Asp Gly Ala Thr His Thr Leu Pro 1700 1705 1710Ser Thr Thr Gly Asn Leu Ala Ala Val Ser Asp Trp Val Met Ser 1715 1720 1725Thr Val Pro Val Ala Pro Pro Arg Arg Arg Arg Gly Arg Asn Leu 1730 1735 1740Thr Val Thr Cys Asp Glu Arg Glu Gly Asn Ile Thr Pro Met Ala 1745 1750 1755Ser Val Arg Phe Phe Arg Ala Glu Leu Cys Pro Val Val Gln Glu 1760 1765 1770Thr Ala Glu Thr Arg Asp Thr Ala Met Ser Leu Gln Ala Pro Pro 1775 1780 1785Ser Thr Ala Thr Glu Pro Asn His Pro Pro Ile Ser Phe Gly Ala 1790 1795 1800Ser Ser Glu Thr Phe Pro Ile Thr Phe Gly Asp Phe Asn Glu Gly 1805 1810 1815Glu Ile Glu Ser Leu Ser Ser Glu Leu Leu Thr Phe Gly Asp Phe 1820 1825 1830Leu Pro Gly Glu Val Asp Asp Leu Thr Asp Ser Asp Trp Ser Thr 1835 1840 1845Cys Ser Asp Thr Asp Asp Glu Leu Leu Asp Arg Ala Gly Gly Tyr 1850 1855 1860Ile Phe Ser Ser Asp Thr Gly Pro Gly His Leu Gln Gln Lys Ser 1865 1870 1875Val Arg Gln Ser Val Leu Pro Val Asn Thr Leu Glu Glu Val His 1880 1885 1890Glu Glu Lys Cys Tyr Pro Pro Lys Leu Asp Glu Ala Lys Glu Gln 1895 1900 1905Leu Leu Leu Lys Lys Leu Gln Glu Ser Ala Ser Met Ala Asn Arg 1910 1915 1920Ser Arg Tyr Gln Ser Arg Lys Val Glu Asn Met Lys Ala Ala Ile 1925 1930 1935Ile Gln Arg Leu Lys Arg Gly Cys Arg Leu Tyr Leu Met Ser Glu 1940 1945 1950Thr Pro Lys Val Pro Thr Tyr Arg Thr Thr Tyr Pro Ala Pro Val 1955 1960 1965Tyr Ser Pro Pro Ile Asn Val Arg Leu Ser Asn Pro Glu Ser Ala 1970 1975 1980Val Ala Ala Cys Asn Glu Phe Leu Ala Arg Asn Tyr Pro Thr Val 1985 1990 1995Ser Ser Tyr Gln Ile Thr Asp Glu Tyr Asp Ala Tyr Leu Asp Met 2000 2005 2010Val Asp Gly Ser Glu Ser Cys Leu Asp Arg Ala Thr Phe Asn Pro 2015 2020 2025Ser Lys Leu Arg Ser Tyr Pro Lys Gln His Ala Tyr His Ala Pro 2030 2035 2040Ser Ile Arg Ser Ala Val Pro Ser Pro Phe Gln Asn Thr Leu Gln 2045 2050 2055Asn Val Leu Ala Ala Ala Thr Lys Arg Asn Cys Asn Val Thr Gln 2060 2065 2070Met Arg Glu Leu Pro Thr Leu Asp Ser Ala Val Phe Asn Val Glu 2075 2080 2085Cys Phe Lys Lys Phe Ala Cys Asn Gln Glu Tyr Trp Glu Glu Phe 2090 2095 2100Ala Ala Ser Pro Ile Arg Ile Thr Thr Glu Asn Leu Ala Thr Tyr 2105 2110 2115Val Thr Lys Leu Lys Gly Pro Lys Ala Ala Ala Leu Phe Ala Lys 2120 2125 2130Thr His Asn Leu Leu Pro Leu Gln Glu Val Pro Met Asp Arg Phe 2135 2140 2145Thr Val Asp Met Lys Arg Asp Val Lys Val Thr Pro Gly Thr Lys 2150 2155 2160His Thr Glu Glu Arg Pro Lys Val Gln Val Ile Gln Ala Ala Glu 2165 2170 2175Pro Leu Ala Thr Ala Tyr Leu Cys Gly Ile His Arg Glu Leu Val 2180 2185 2190Arg Arg Leu Asn Ala Val Leu Leu Pro Asn Val His Thr Leu Phe 2195 2200 2205Asp Met Ser Ala Glu Asp Phe Asp Ala Ile Ile Ala Ala His Phe 2210 2215 2220Lys Pro Gly Asp Thr Val Leu Glu Thr Asp Ile Ala Ser Phe Asp 2225 2230 2235Lys Ser Gln Asp Asp Ser Leu Ala Leu Thr Ala Leu Met Leu Leu 2240 2245 2250Glu Asp Leu Gly Val Asp His Ser Leu Leu Asp Leu Ile Glu Ala 2255 2260 2265Ala Phe Gly Glu Ile Ser Ser Cys His Leu Pro Thr Gly Thr Arg 2270 2275 2280Phe Lys Phe Gly Ala Met Met Lys Ser Gly Met Phe Leu Thr Leu 2285 2290 2295Phe Val Asn Thr Leu Leu Asn Ile Thr Ile Ala Ser Arg Val Leu 2300 2305 2310Glu Asp Arg Leu Thr Lys Ser Ala Cys Ala Ala Phe Ile Gly Asp 2315 2320 2325Asp Asn Ile Ile His Gly Val Val Ser Asp Glu Leu Met Ala Ala 2330 2335 2340Arg Cys Ala Thr Trp Met Asn Met Glu Val Lys Ile Ile Asp Ala 2345 2350 2355Val Val Ser Leu Lys Ala Pro Tyr Phe Cys Gly Gly Phe Ile Leu 2360 2365 2370His Asp Thr Val Thr Gly Thr Ala Cys Arg Val Ala Asp Pro Leu 2375 2380 2385Lys Arg Leu Phe Lys Leu Gly Lys Pro Leu Ala Ala Gly Asp Glu 2390 2395 2400Gln Asp Glu Asp Arg Arg Arg Ala Leu Ala Asp Glu Val Ile Arg 2405 2410 2415Trp Gln Arg Thr Gly Leu Ile Asp Glu Leu Glu Lys Ala Val Tyr 2420 2425 2430Ser Arg Tyr Glu Val Gln Gly Ile Ser Val Val Val Met Ser Met 2435 2440 2445Ala Thr Phe Ala Ser Ser Arg Ser Asn Phe Glu Lys Leu Arg Gly 2450 2455 2460Pro Val Ile Thr Leu Tyr Gly Gly Pro Lys 2465 2470312473PRTChikungunya virus 31Met Asp Pro Val Tyr Val Asp Ile Asp Ala Asp Ser Ala Phe Leu Lys1 5 10 15Ala Leu Gln Arg Ala Tyr Pro Met Phe Glu Val Glu Pro Arg Gln Val 20 25 30Thr Pro Asn Asp His Ala Asn Ala Arg Ala Phe Ser His Leu Ala Ile 35 40 45Lys Leu Ile Glu Gln Glu Ile Asp Pro Asp Ser Thr Ile Leu Asp Ile 50 55 60Gly Ser Ala Pro Ala Arg Arg Met Met Ser Asp Arg Lys Tyr His Cys65 70 75 80Val Cys Pro Met Arg Ser Ala Glu Asp Pro Glu Arg Leu Ala Asn Tyr 85 90 95Ala Arg Lys Leu Ala Ser Ala Ala Gly Lys Val Leu Asp Arg Asn Ile 100 105 110Ser Gly Lys Ile Gly Asp Leu Gln Ala Val Met Ala Val Pro Asp Thr 115 120 125Glu Thr Pro Thr Phe Cys Leu His Thr Asp Val Ser Cys Arg Gln Arg 130 135 140Ala Asp Val Ala Ile Tyr Gln Asp Val Tyr Ala Val His Ala Pro Thr145 150 155 160Ser Leu Tyr His Gln Ala Ile Lys Gly Val Arg Val Ala Tyr Trp Val 165 170 175Gly Phe Asp Thr Thr Pro Phe Met Tyr Asn Ala Met Ala Gly Ala Tyr 180 185 190Pro Ser Tyr Ser Thr Asn Trp Ala Asp Glu Gln Val Leu Lys Ala Lys 195 200 205Asn Ile Gly Leu Cys Ser Thr Asp Leu Thr Glu Gly Arg Arg Gly Lys 210 215 220Leu Ser Ile Met Arg Gly Lys Lys Leu Lys Pro Cys Asp Arg Val Leu225 230 235 240Phe Ser Val Gly Ser Thr Leu Tyr Pro Glu Ser Arg Lys Leu Leu Lys 245 250 255Ser Trp His Leu Pro Ser Val Phe His Leu Lys Gly Lys Leu Ser Phe 260 265 270Thr Cys Arg Cys Asp Thr Val Val Ser Cys Glu Gly Tyr Val Val Lys 275 280 285Arg Ile Thr Met Ser Pro Gly Leu Tyr Gly Lys Thr Thr Gly Tyr Ala 290 295 300Val Thr His His Ala Asp Gly Phe Leu Met Cys Lys Thr Thr Asp Thr305 310 315 320Val Asp Gly Glu Arg Val Ser Phe Ser Val Cys Thr Tyr Val Pro Ala 325 330 335Thr Ile Cys Asp Gln Met Thr Gly Ile Leu Ala Thr Glu Val Thr Pro 340 345 350Glu Asp Ala Gln Lys Leu Leu Val Gly Leu Asn Gln Arg Ile Val Val 355 360 365Asn Gly Arg Thr Gln Arg Asn Thr Asn Thr Met Lys Asn Tyr Leu Leu 370 375 380Pro Val Val Ala Gln Ala Phe Ser Lys Trp Ala Lys Glu Cys Arg Lys385 390 395 400Asp Met Glu Asp Glu Lys Leu Leu Gly Val Arg Glu Arg Thr Leu Thr 405 410 415Cys Cys Cys Leu Trp Ala Phe Lys Lys Gln Lys Thr His Thr Val Tyr 420 425 430Lys Arg Pro Asp Thr Gln Ser Ile Gln Lys Val Gln Ala Glu Phe Asp 435 440 445Ser Phe Val Val Pro Ser Leu Trp Ser Ser Gly Leu Ser Ile Pro Leu 450 455 460Arg Thr Arg Ile Lys Trp Leu Leu Ser Lys Val Pro Lys Thr Asp Leu465 470 475 480Ile Pro Tyr Ser Gly Asp Ala Arg Glu Ala Arg Asp Ala Glu Lys Glu 485 490 495Ala Glu Glu Glu Arg Glu Ala Glu Leu Thr Arg Glu Ala Leu Pro Pro 500 505 510Leu Gln Ala Ala Gln Glu Asp Val Gln Val Glu Ile Asp Val Glu Gln 515 520 525Leu Glu Asp Arg Ala Gly Ala Gly Ile Ile Glu Thr Pro Arg Gly Ala 530 535 540Ile Lys Val Thr Ala Gln Pro Thr Asp His Val Val Gly Glu Tyr Leu545 550 555 560Val Leu Ser Pro Gln Thr Val Leu Arg Ser Gln Lys Leu Ser Leu Ile 565 570 575His Ala Leu Ala Glu Gln Val Lys Thr Cys Thr His Asn Gly Arg Ala 580 585 590Gly Arg Tyr Ala Val Glu Ala Tyr Asp Gly Arg Val Leu Val Pro Ser 595 600 605Gly Tyr Ala Ile Ser Pro Glu Asp Phe Gln Ser Leu Ser Glu Ser Ala 610 615 620Thr Met Val Tyr Asn Glu Arg Glu Phe Val Asn Arg Lys Leu His His625 630 635 640Ile Ala Met His Gly Pro Ala Leu Asn Thr Asp Glu Glu Ser Tyr Glu 645 650 655Leu Val Arg Ala Glu Arg Thr Glu His Glu Tyr Val Tyr Asp Val Asp 660 665 670Gln Arg Arg Cys Cys Lys Lys Glu Glu Ala Ala Gly Leu Val Leu Val 675 680 685Gly Asp Leu Thr Asn Pro Pro Tyr His Glu Phe Ala Tyr Glu Gly Leu 690 695 700Lys Ile Arg Pro Ala Cys Pro Tyr Lys Ile Ala Val Ile Gly Val Phe705 710 715 720Gly Val Pro Gly Ser Gly Lys Ser Ala Ile Ile Lys Asn Leu Val Thr 725 730 735Arg Gln Asp Leu Val Thr Ser Gly Lys Lys Glu Asn Cys Gln Glu Ile 740 745 750Thr Thr Asp Val Met Arg Gln Arg Gly Leu Glu Ile Ser Ala Arg Thr 755 760 765Val Asp Ser Leu Leu Leu Asn Gly Cys Asn Arg Pro Val Asp Val Leu 770 775 780Tyr Val Asp Glu Ala Phe Ala Cys His Ser Gly Thr Leu Leu Ala Leu785 790 795 800Ile Ala Leu Val Arg Pro Arg Gln Lys Val Val Leu Cys Gly Asp Pro 805 810 815Lys Gln Cys Gly Phe Phe Asn Met Met Gln Met Lys Val Asn Tyr Asn 820 825 830His Asn Ile Cys Thr Gln Val Tyr His Lys Ser Ile Ser Arg Arg Cys 835 840 845Thr Leu Pro Val Thr Ala Ile Val Ser Ser Leu His Tyr Glu Gly Lys 850 855 860Met Arg Thr Thr Asn Glu Tyr Asn Lys Pro Ile Val Val Asp Thr Thr865 870 875 880Gly Ser Thr Lys Pro Asp Pro Gly Asp Leu Val Leu Thr Cys Phe Arg 885 890 895Gly Trp Val Lys Gln Leu Gln Ile Asp Tyr Arg Gly Tyr Glu Val Met 900 905 910Thr Ala Ala Ala Ser Gln Gly Leu Thr Arg Lys Gly Val Tyr Ala Val 915 920 925Arg Gln Lys Val Asn Glu Asn Pro Leu Tyr Ala Ser Thr Ser Glu His 930 935 940Val Asn Val Leu Leu Thr Arg Thr Glu Gly Lys Leu Val Trp Lys Thr945 950 955 960Leu Ser Gly Asp Pro Trp Ile Lys Thr Leu Gln Asn Pro Pro Lys Gly 965 970 975Asn Phe Lys Ala Thr Ile Lys Glu Trp Glu Val Glu His Ala Ser Ile 980 985 990Met Ala Gly Ile Cys Ser His Gln Met Thr Phe Asp Thr Phe Gln Asn 995 1000 1005Lys Ala Asn Val Cys Trp Ala Lys Ser Leu Val Pro Ile Leu Glu 1010 1015 1020Thr Ala Gly Ile Lys Leu Asn Asp Arg Gln Trp Ser Gln Ile Ile 1025 1030 1035Gln Ala Phe Lys Glu Asp Lys Ala Tyr Ser Pro Glu Val Ala Leu 1040 1045 1050Asn Glu Ile Cys Thr Arg Met Tyr Gly Val Asp Leu Asp Ser Gly 1055 1060 1065Leu Phe Ser Lys Pro Leu Val Ser Val Tyr Tyr Ala Asp Asn His 1070 1075 1080Trp Asp Asn Arg Pro Gly Gly Lys Met Phe Gly Phe Asn Pro Glu 1085 1090 1095Ala Ala Ser Ile

Leu Glu Arg Lys Tyr Pro Phe Thr Lys Gly Lys 1100 1105 1110Trp Asn Ile Asn Lys Gln Ile Cys Val Thr Thr Arg Arg Ile Glu 1115 1120 1125Asp Phe Asn Pro Thr Thr Asn Ile Ile Pro Ala Asn Arg Arg Leu 1130 1135 1140Pro His Ser Leu Val Ala Glu His Arg Pro Val Lys Gly Glu Arg 1145 1150 1155Met Glu Trp Leu Val Asn Lys Ile Asn Gly His His Val Leu Leu 1160 1165 1170Val Ser Gly Tyr Asn Leu Ala Leu Pro Thr Lys Arg Val Thr Trp 1175 1180 1185Val Ala Pro Leu Gly Val Arg Gly Ala Asp Tyr Thr Tyr Asn Leu 1190 1195 1200Glu Leu Gly Leu Pro Ala Thr Leu Gly Arg Tyr Asp Leu Val Val 1205 1210 1215Ile Asn Ile His Thr Pro Phe Arg Ile His His Tyr Gln Gln Cys 1220 1225 1230Val Asp His Ala Met Lys Leu Gln Met Leu Gly Gly Asp Ser Leu 1235 1240 1245Arg Leu Leu Lys Pro Gly Gly Ser Leu Leu Ile Arg Ala Tyr Gly 1250 1255 1260Tyr Ala Asp Arg Thr Ser Glu Arg Val Ile Cys Val Leu Gly Arg 1265 1270 1275Lys Phe Arg Ser Ser Arg Ala Leu Lys Pro Pro Cys Val Thr Ser 1280 1285 1290Asn Thr Glu Met Phe Phe Leu Phe Ser Asn Phe Asp Asn Gly Arg 1295 1300 1305Arg Asn Phe Thr Thr His Val Met Asn Asn Gln Leu Asn Ala Ala 1310 1315 1320Phe Val Gly Gln Val Thr Arg Ala Gly Cys Ala Pro Ser Tyr Arg 1325 1330 1335Val Lys Arg Met Asp Ile Ala Lys Asn Asp Glu Glu Cys Val Val 1340 1345 1350Asn Ala Ala Asn Pro Arg Gly Leu Pro Gly Asp Gly Val Cys Lys 1355 1360 1365Ala Val Tyr Lys Lys Trp Pro Glu Ser Phe Lys Asn Ser Ala Thr 1370 1375 1380Pro Val Gly Thr Ala Lys Thr Val Met Cys Gly Thr Tyr Pro Val 1385 1390 1395Ile His Ala Val Gly Pro Asn Phe Ser Asn Tyr Ser Glu Ser Glu 1400 1405 1410Gly Asp Arg Glu Leu Ala Ala Ala Tyr Arg Glu Val Ala Lys Glu 1415 1420 1425Val Thr Arg Leu Gly Val Asn Ser Val Ala Ile Pro Leu Leu Ser 1430 1435 1440Thr Gly Val Tyr Ser Gly Gly Lys Asp Arg Leu Thr Gln Ser Leu 1445 1450 1455Asn His Leu Phe Thr Ala Met Asp Ser Thr Asp Ala Asp Val Val 1460 1465 1470Ile Tyr Cys Arg Asp Lys Glu Trp Glu Lys Lys Ile Ser Glu Ala 1475 1480 1485Ile Gln Met Arg Thr Gln Val Glu Leu Leu Asp Glu His Ile Ser 1490 1495 1500Ile Asp Cys Asp Ile Val Arg Val His Pro Asp Ser Ser Leu Ala 1505 1510 1515Gly Arg Lys Gly Tyr Ser Thr Thr Glu Gly Ala Leu Tyr Ser Tyr 1520 1525 1530Leu Glu Gly Thr Arg Phe His Gln Thr Ala Val Asp Met Ala Glu 1535 1540 1545Ile His Thr Met Trp Pro Lys Gln Thr Glu Ala Asn Glu Gln Val 1550 1555 1560Cys Leu Tyr Ala Leu Gly Glu Ser Ile Glu Ser Ile Arg Gln Lys 1565 1570 1575Cys Pro Val Asp Asp Ala Asp Ala Ser Ser Pro Pro Lys Thr Val 1580 1585 1590Pro Cys Leu Cys Arg Tyr Ala Met Thr Pro Glu Arg Val Thr Arg 1595 1600 1605Leu Arg Met Asn His Val Thr Ser Ile Ile Val Cys Ser Ser Phe 1610 1615 1620Pro Leu Pro Lys Tyr Lys Ile Glu Gly Val Gln Lys Val Lys Cys 1625 1630 1635Ser Lys Val Met Leu Phe Asp His Asn Val Pro Ser Arg Val Ser 1640 1645 1650Pro Arg Glu Tyr Arg Ser Ser Gln Glu Ser Ala Gln Glu Ala Ser 1655 1660 1665Thr Ile Thr Ser Leu Thr His Ser Gln Phe Asp Leu Ser Val Asp 1670 1675 1680Gly Glu Ile Leu Pro Val Pro Pro Asp Leu Asp Ala Asp Ala Pro 1685 1690 1695Ala Leu Glu Pro Ala Leu Asp Asp Gly Ala Thr His Thr Leu Pro 1700 1705 1710Ser Thr Thr Gly Asn Leu Ala Ala Val Ser Asp Trp Val Met Ser 1715 1720 1725Thr Val Pro Val Ala Pro Pro Arg Arg Arg Arg Gly Arg Asn Leu 1730 1735 1740Thr Val Thr Cys Asp Glu Arg Glu Gly Asn Ile Thr Pro Met Ala 1745 1750 1755Ser Val Arg Phe Phe Arg Ala Glu Leu Cys Pro Val Val Gln Glu 1760 1765 1770Thr Ala Glu Thr Arg Asp Thr Ala Met Ser Leu Gln Ala Pro Pro 1775 1780 1785Ser Thr Ala Thr Glu Pro Asn His Pro Pro Ile Ser Phe Gly Ala 1790 1795 1800Ser Ser Glu Thr Phe Pro Ile Thr Phe Gly Asp Phe Asn Glu Gly 1805 1810 1815Glu Ile Glu Ser Leu Ser Ser Glu Leu Leu Thr Phe Gly Asp Phe 1820 1825 1830Leu Pro Gly Glu Val Asp Asp Leu Thr Asp Ser Asp Trp Ser Thr 1835 1840 1845Cys Ser Asp Thr Asp Asp Glu Leu Leu Asp Arg Ala Gly Gly Tyr 1850 1855 1860Ile Phe Ser Ser Asp Thr Gly Pro Gly His Leu Gln Gln Lys Ser 1865 1870 1875Val Arg Gln Ser Val Leu Pro Val Asn Thr Leu Glu Glu Val His 1880 1885 1890Glu Glu Lys Cys Tyr Pro Pro Lys Leu Asp Glu Ala Lys Glu Gln 1895 1900 1905Leu Leu Leu Lys Lys Leu Gln Glu Ser Ala Ser Met Ala Asn Arg 1910 1915 1920Ser Arg Tyr Gln Ser Arg Lys Val Glu Asn Met Lys Ala Ala Ile 1925 1930 1935Ile Gln Arg Leu Lys Arg Gly Cys Arg Leu Tyr Leu Met Ser Glu 1940 1945 1950Thr Pro Lys Val Pro Thr Tyr Arg Thr Thr Tyr Pro Ala Pro Val 1955 1960 1965Tyr Ser Pro Pro Ile Asn Val Arg Leu Ser Asn Pro Glu Ser Ala 1970 1975 1980Val Ala Ala Cys Asn Glu Phe Leu Ala Arg Asn Tyr Pro Thr Val 1985 1990 1995Ser Ser Tyr Gln Ile Thr Asp Glu Tyr Asp Ala Tyr Leu Asp Met 2000 2005 2010Val Asp Gly Ser Glu Ser Cys Leu Asp Arg Ala Thr Phe Asn Pro 2015 2020 2025Ser Lys Leu Arg Ser Tyr Pro Lys Gln His Ala Tyr His Ala Pro 2030 2035 2040Ser Ile Arg Ser Ala Val Pro Ser Pro Phe Gln Asn Thr Leu Gln 2045 2050 2055Asn Val Leu Ala Ala Ala Thr Lys Arg Asn Cys Asn Val Thr Gln 2060 2065 2070Met Arg Glu Leu Pro Thr Leu Asp Ser Ala Val Phe Asn Val Glu 2075 2080 2085Cys Phe Lys Lys Phe Ala Cys Asn Gln Glu Tyr Trp Glu Glu Phe 2090 2095 2100Ala Ala Ser Pro Ile Arg Ile Thr Thr Glu Asn Leu Ala Thr Tyr 2105 2110 2115Val Thr Lys Leu Lys Gly Pro Lys Ala Ala Ala Leu Phe Ala Lys 2120 2125 2130Thr His Asn Leu Leu Pro Leu Gln Glu Val Pro Met Asp Arg Phe 2135 2140 2145Thr Val Asp Met Lys Arg Asp Val Lys Val Thr Pro Gly Thr Lys 2150 2155 2160His Thr Glu Glu Arg Pro Lys Val Gln Val Ile Gln Ala Ala Glu 2165 2170 2175Pro Leu Ala Thr Ala Tyr Leu Cys Gly Ile His Arg Glu Leu Val 2180 2185 2190Arg Arg Leu Asn Ala Val Leu Leu Pro Asn Val His Thr Leu Phe 2195 2200 2205Asp Met Ser Ala Glu Asp Phe Asp Ala Ile Ile Ala Ala His Phe 2210 2215 2220Lys Pro Gly Asp Thr Val Leu Glu Thr Asp Ile Ala Ser Phe Asp 2225 2230 2235Lys Ser Gln Asp Asp Ser Leu Ala Leu Thr Ala Leu Met Leu Leu 2240 2245 2250Glu Asp Leu Gly Val Asp His Ser Leu Leu Asp Leu Ile Glu Ala 2255 2260 2265Ala Phe Gly Glu Ile Ser Ser Cys His Leu Pro Thr Gly Thr Arg 2270 2275 2280Phe Lys Phe Gly Ala Met Met Lys Ser Gly Met Phe Leu Thr Leu 2285 2290 2295Phe Val Asn Thr Leu Leu Asn Ile Thr Ile Ala Ser Arg Val Leu 2300 2305 2310Glu Asp Arg Leu Thr Lys Ser Ala Cys Ala Ala Phe Ile Gly Asp 2315 2320 2325Asp Asn Ile Ile His Gly Val Val Ser Asp Glu Leu Met Ala Ala 2330 2335 2340Arg Cys Ala Thr Trp Met Asn Met Glu Val Lys Ile Ile Asp Ala 2345 2350 2355Val Val Ser Leu Lys Ala Pro Tyr Phe Cys Gly Gly Phe Ile Leu 2360 2365 2370His Asp Thr Val Thr Gly Thr Ala Cys Arg Val Ala Asp Pro Leu 2375 2380 2385Lys Arg Leu Phe Lys Leu Gly Lys Pro Leu Ala Ala Gly Asp Glu 2390 2395 2400Gln Asp Glu Asp Arg Arg Arg Ala Leu Ala Asp Glu Val Ile Arg 2405 2410 2415Trp Gln Arg Thr Gly Leu Ile Asp Glu Leu Glu Lys Ala Val Tyr 2420 2425 2430Ser Arg Tyr Glu Val Gln Gly Ile Ser Val Val Val Met Ser Met 2435 2440 2445Ala Thr Phe Ala Ser Ser Arg Ser Asn Phe Glu Lys Leu Arg Gly 2450 2455 2460Pro Val Ile Thr Leu Tyr Gly Gly Pro Lys 2465 2470322473PRTChikungunya virus 32Met Asp Pro Val Tyr Val Asp Ile Asp Ala Asp Ser Ala Phe Leu Lys1 5 10 15Ala Leu Gln Arg Ala Tyr Pro Met Phe Glu Val Glu Pro Arg Gln Val 20 25 30Thr Pro Asn Asp His Ala Asn Ala Arg Ala Phe Ser His Leu Ala Ile 35 40 45Lys Leu Ile Glu Gln Glu Ile Asp Pro Asp Ser Thr Ile Leu Asp Ile 50 55 60Gly Ser Ala Pro Ala Arg Arg Met Met Ser Asp Arg Lys Tyr His Cys65 70 75 80Val Cys Pro Met Arg Ser Ala Glu Asp Pro Glu Arg Leu Ala Asn Tyr 85 90 95Ala Arg Lys Leu Ala Ser Ala Ala Gly Lys Val Leu Asp Arg Asn Ile 100 105 110Ser Gly Lys Ile Gly Asp Leu Gln Ala Val Met Ala Val Pro Asp Thr 115 120 125Glu Thr Pro Thr Phe Cys Leu His Thr Asp Val Ser Cys Arg Gln Arg 130 135 140Ala Asp Val Ala Ile Tyr Gln Asp Val Tyr Ala Val His Ala Pro Thr145 150 155 160Ser Leu Tyr His Gln Ala Ile Lys Gly Val Arg Val Ala Tyr Trp Val 165 170 175Gly Phe Asp Thr Thr Pro Phe Met Tyr Asn Ala Met Ala Gly Ala Tyr 180 185 190Pro Ser Tyr Ser Thr Asn Trp Ala Asp Glu Gln Val Leu Lys Ala Lys 195 200 205Asn Ile Gly Leu Cys Ser Thr Asp Leu Thr Glu Gly Arg Arg Gly Lys 210 215 220Leu Ser Ile Met Arg Gly Lys Lys Leu Lys Pro Cys Asp Arg Val Leu225 230 235 240Phe Ser Val Gly Ser Thr Leu Tyr Pro Glu Ser Arg Lys Leu Leu Lys 245 250 255Ser Trp His Leu Pro Ser Val Phe His Leu Lys Gly Lys Leu Ser Phe 260 265 270Thr Cys Arg Cys Asp Thr Val Val Ser Cys Glu Gly Tyr Val Val Lys 275 280 285Arg Ile Thr Met Ser Pro Gly Leu Tyr Gly Lys Thr Thr Gly Tyr Ala 290 295 300Val Thr His His Ala Asp Gly Phe Leu Met Cys Lys Thr Thr Asp Thr305 310 315 320Val Asp Gly Glu Arg Val Ser Phe Ser Val Cys Thr Tyr Val Pro Ala 325 330 335Thr Ile Cys Asp Gln Met Thr Gly Ile Leu Ala Thr Glu Val Thr Pro 340 345 350Glu Asp Ala Gln Lys Leu Leu Val Gly Leu Asn Gln Arg Ile Val Val 355 360 365Asn Gly Arg Thr Gln Arg Asn Thr Asn Thr Met Lys Asn Tyr Leu Leu 370 375 380Pro Val Val Ala Gln Ala Phe Ser Lys Trp Ala Lys Glu Cys Arg Lys385 390 395 400Asp Met Glu Asp Glu Lys Leu Leu Gly Val Arg Glu Arg Thr Leu Thr 405 410 415Cys Cys Cys Leu Trp Ala Phe Lys Lys Gln Lys Thr His Thr Val Tyr 420 425 430Lys Arg Pro Asp Thr Gln Ser Ile Gln Lys Val Gln Ala Glu Phe Asp 435 440 445Ser Phe Val Val Pro Ser Leu Trp Ser Ser Gly Leu Ser Ile Pro Leu 450 455 460Arg Thr Arg Ile Lys Trp Leu Leu Ser Lys Val Pro Lys Thr Asp Leu465 470 475 480Ile Pro Tyr Ser Gly Asp Ala Arg Glu Ala Arg Asp Ala Glu Lys Glu 485 490 495Ala Glu Glu Glu Arg Glu Ala Glu Leu Thr Arg Glu Ala Leu Pro Pro 500 505 510Leu Gln Ala Ala Gln Glu Asp Val Gln Val Glu Ile Asp Val Glu Gln 515 520 525Leu Glu Asp Arg Ala Gly Ala Gly Ile Ile Glu Thr Pro Arg Gly Ala 530 535 540Ile Lys Val Thr Ala Gln Pro Thr Asp His Val Val Gly Glu Tyr Leu545 550 555 560Val Leu Ser Pro Gln Thr Val Leu Arg Ser Gln Lys Leu Ser Leu Ile 565 570 575His Ala Leu Ala Glu Gln Val Lys Thr Cys Thr His Asn Gly Arg Ala 580 585 590Gly Arg Tyr Ala Val Glu Ala Tyr Asp Gly Arg Val Leu Val Pro Ser 595 600 605Gly Tyr Ala Ile Ser Pro Glu Asp Phe Gln Ser Leu Ser Glu Ser Ala 610 615 620Thr Met Val Tyr Asn Glu Arg Glu Phe Val Asn Arg Lys Leu His His625 630 635 640Ile Ala Met His Gly Pro Ala Leu Asn Thr Asp Glu Glu Ser Tyr Glu 645 650 655Leu Val Arg Ala Glu Arg Thr Glu His Glu Tyr Val Tyr Asp Val Asp 660 665 670Gln Arg Arg Cys Cys Lys Lys Glu Glu Ala Ala Gly Leu Val Leu Val 675 680 685Gly Asp Leu Thr Asn Pro Pro Tyr His Glu Phe Ala Tyr Glu Gly Leu 690 695 700Lys Ile Arg Pro Ala Cys Pro Tyr Lys Ile Ala Val Ile Gly Val Phe705 710 715 720Gly Val Pro Gly Ser Gly Lys Ser Ala Ile Ile Lys Asn Leu Val Thr 725 730 735Arg Gln Asp Leu Val Thr Ser Gly Lys Lys Glu Asn Cys Gln Glu Ile 740 745 750Thr Thr Asp Val Met Arg Gln Arg Gly Leu Glu Ile Ser Ala Arg Thr 755 760 765Val Asp Ser Leu Leu Leu Asn Gly Cys Asn Arg Pro Val Asp Val Leu 770 775 780Tyr Val Asp Glu Ala Phe Ala Cys His Ser Gly Thr Leu Leu Ala Leu785 790 795 800Ile Ala Leu Val Arg Pro Arg Gln Lys Val Val Leu Cys Gly Asp Pro 805 810 815Lys Gln Cys Gly Phe Phe Asn Met Met Gln Met Lys Val Asn Tyr Asn 820 825 830His Asn Ile Cys Thr Gln Val Tyr His Lys Ser Ile Ser Arg Arg Cys 835 840 845Thr Leu Pro Val Thr Ala Ile Val Ser Ser Leu His Tyr Glu Gly Lys 850 855 860Met Arg Thr Thr Asn Glu Tyr Asn Lys Pro Ile Val Val Asp Thr Thr865 870 875 880Gly Ser Thr Lys Pro Asp Pro Gly Asp Leu Val Leu Thr Cys Phe Arg 885 890 895Gly Trp Val Lys Gln Leu Gln Ile Asp Tyr Arg Gly Tyr Glu Val Met 900 905 910Thr Ala Ala Ala Ser Gln Gly Leu Thr Arg Lys Gly Val Tyr Ala Val 915 920 925Arg Gln Lys Val Asn Glu Asn Pro Leu Tyr Ala Ser Thr Ser Glu His 930 935 940Val Asn Val Leu Leu Thr Arg Thr Glu Gly Lys Leu Val Trp Lys Thr945 950 955 960Leu Ser Gly Asp Pro Trp Ile Lys Thr Leu Gln Asn Pro Pro Lys Gly 965 970 975Asn Phe Lys Ala Thr Ile Lys Glu Trp Glu Val Glu His Ala Ser Ile 980 985 990Met Ala Gly Ile Cys Ser His Gln Met Thr Phe Asp Thr Phe Gln Asn 995 1000 1005Lys Ala Asn Val Cys Trp Ala Lys Ser Leu Val Pro Ile Leu Glu 1010 1015 1020Thr Ala Gly Ile Lys Leu Asn Asp Arg Gln Trp Ser Gln Ile Ile 1025 1030 1035Gln Ala Phe Lys Glu Asp Lys Ala Tyr Ser Pro Glu Val Ala Leu 1040 1045 1050Asn Glu Ile Cys Thr Arg Met Tyr Gly Val Asp Leu Asp Ser Gly 1055 1060 1065Leu Phe Ser Lys Pro Leu Val Ser Val Tyr Tyr Ala Asp

Asn His 1070 1075 1080Trp Asp Asn Arg Pro Gly Gly Lys Met Phe Gly Phe Asn Pro Glu 1085 1090 1095Ala Ala Ser Ile Leu Glu Arg Lys Tyr Pro Phe Thr Lys Gly Lys 1100 1105 1110Trp Asn Ile Asn Lys Gln Ile Cys Val Thr Thr Arg Arg Ile Glu 1115 1120 1125Asp Phe Asn Pro Thr Thr Asn Ile Ile Pro Ala Asn Arg Arg Leu 1130 1135 1140Pro His Ser Leu Val Ala Glu His Arg Pro Val Lys Gly Glu Arg 1145 1150 1155Met Glu Trp Leu Val Asn Lys Ile Asn Gly His His Val Leu Leu 1160 1165 1170Val Ser Gly Tyr Asn Leu Ala Leu Pro Thr Lys Arg Val Thr Trp 1175 1180 1185Val Ala Pro Leu Gly Val Arg Gly Ala Asp Tyr Thr Tyr Asn Leu 1190 1195 1200Glu Leu Gly Leu Pro Ala Thr Leu Gly Arg Tyr Asp Leu Val Val 1205 1210 1215Ile Asn Ile His Thr Pro Phe Arg Ile His His Tyr Gln Gln Cys 1220 1225 1230Val Asp His Ala Met Lys Leu Gln Met Leu Gly Gly Asp Ser Leu 1235 1240 1245Arg Leu Leu Lys Pro Gly Gly Ser Leu Leu Ile Arg Ala Tyr Gly 1250 1255 1260Tyr Ala Asp Arg Thr Ser Glu Arg Val Ile Cys Val Leu Gly Arg 1265 1270 1275Lys Phe Arg Ser Ser Arg Ala Leu Lys Pro Pro Cys Val Thr Ser 1280 1285 1290Asn Thr Glu Met Phe Phe Leu Phe Ser Asn Phe Asp Asn Gly Arg 1295 1300 1305Arg Asn Phe Thr Thr His Val Met Asn Asn Gln Leu Asn Ala Ala 1310 1315 1320Phe Val Gly Gln Val Thr Arg Ala Gly Cys Ala Pro Ser Tyr Arg 1325 1330 1335Val Lys Arg Met Asp Ile Ala Lys Asn Asp Glu Glu Cys Val Val 1340 1345 1350Asn Ala Ala Asn Pro Arg Gly Leu Pro Gly Asp Gly Val Cys Lys 1355 1360 1365Ala Val Tyr Lys Lys Trp Pro Glu Ser Phe Lys Asn Ser Ala Thr 1370 1375 1380Pro Val Gly Thr Ala Lys Thr Val Met Cys Gly Thr Tyr Pro Val 1385 1390 1395Ile His Ala Val Gly Pro Asn Phe Ser Asn Tyr Ser Glu Ser Glu 1400 1405 1410Gly Asp Arg Glu Leu Ala Ala Ala Tyr Arg Glu Val Ala Lys Glu 1415 1420 1425Val Thr Arg Leu Gly Val Asn Ser Val Ala Ile Pro Leu Leu Ser 1430 1435 1440Thr Gly Val Tyr Ser Gly Gly Lys Asp Arg Leu Thr Gln Ser Leu 1445 1450 1455Asn His Leu Phe Thr Ala Met Asp Ser Thr Asp Ala Asp Val Val 1460 1465 1470Ile Tyr Cys Arg Asp Lys Glu Trp Glu Lys Lys Ile Ser Glu Ala 1475 1480 1485Ile Gln Met Arg Thr Gln Val Glu Leu Leu Asp Glu His Ile Ser 1490 1495 1500Ile Asp Cys Asp Ile Val Arg Val His Pro Asp Ser Ser Leu Ala 1505 1510 1515Gly Arg Lys Gly Tyr Ser Thr Thr Glu Gly Ala Leu Tyr Ser Tyr 1520 1525 1530Leu Glu Gly Thr Arg Phe His Gln Thr Ala Val Asp Met Ala Glu 1535 1540 1545Ile His Thr Met Trp Pro Lys Gln Thr Glu Ala Asn Glu Gln Val 1550 1555 1560Cys Leu Tyr Ala Leu Gly Glu Ser Ile Glu Ser Ile Arg Gln Lys 1565 1570 1575Cys Pro Val Asp Asp Ala Asp Ala Ser Ser Pro Pro Lys Thr Val 1580 1585 1590Pro Cys Leu Cys Arg Tyr Ala Met Thr Pro Glu Arg Val Thr Arg 1595 1600 1605Leu Arg Met Asn His Val Thr Ser Ile Ile Val Cys Ser Ser Phe 1610 1615 1620Pro Leu Pro Lys Tyr Lys Ile Glu Gly Val Gln Lys Val Lys Cys 1625 1630 1635Ser Lys Val Met Leu Phe Asp His Asn Val Pro Ser Arg Val Ser 1640 1645 1650Pro Arg Glu Tyr Arg Ser Ser Gln Glu Ser Ala Gln Glu Ala Ser 1655 1660 1665Thr Ile Thr Ser Leu Thr His Ser Gln Phe Asp Leu Ser Val Asp 1670 1675 1680Gly Glu Ile Leu Pro Val Pro Ser Asp Leu Asp Ala Asp Ala Pro 1685 1690 1695Ala Leu Glu Pro Ala Leu Asp Asp Gly Ala Thr His Thr Leu Pro 1700 1705 1710Ser Thr Thr Gly Asn Leu Ala Ala Val Ser Asp Trp Val Met Ser 1715 1720 1725Thr Val Pro Val Ala Pro Pro Arg Arg Arg Arg Gly Arg Asn Leu 1730 1735 1740Thr Val Thr Cys Asp Glu Arg Glu Gly Asn Ile Thr Pro Met Ala 1745 1750 1755Ser Val Arg Phe Phe Arg Ala Glu Leu Cys Pro Val Val Gln Glu 1760 1765 1770Thr Ala Glu Thr Arg Asp Thr Ala Met Ser Leu Gln Ala Pro Pro 1775 1780 1785Ser Thr Ala Thr Glu Pro Asn His Pro Pro Ile Ser Phe Gly Ala 1790 1795 1800Ser Ser Glu Thr Phe Pro Ile Thr Phe Gly Asp Phe Asn Glu Gly 1805 1810 1815Glu Ile Glu Ser Leu Ser Ser Glu Leu Leu Thr Phe Gly Asp Phe 1820 1825 1830Leu Pro Gly Glu Val Asp Asp Leu Thr Asp Ser Asp Trp Ser Thr 1835 1840 1845Cys Ser Asp Thr Asp Asp Glu Leu Leu Asp Arg Ala Gly Gly Tyr 1850 1855 1860Ile Phe Ser Ser Asp Thr Gly Pro Gly His Leu Gln Gln Lys Ser 1865 1870 1875Val Arg Gln Ser Val Leu Pro Val Asn Thr Leu Glu Glu Val His 1880 1885 1890Glu Glu Lys Cys Tyr Pro Pro Lys Leu Asp Glu Ala Lys Glu Gln 1895 1900 1905Leu Leu Leu Lys Lys Leu Gln Glu Ser Ala Ser Met Ala Asn Arg 1910 1915 1920Ser Arg Tyr Gln Ser Arg Lys Val Glu Asn Met Lys Ala Ala Ile 1925 1930 1935Ile Gln Arg Leu Lys Arg Gly Cys Arg Leu Tyr Leu Met Ser Glu 1940 1945 1950Thr Pro Lys Val Pro Thr Tyr Arg Thr Thr Tyr Pro Ala Pro Val 1955 1960 1965Tyr Ser Pro Pro Ile Asn Val Arg Leu Ser Asn Pro Glu Ser Ala 1970 1975 1980Val Ala Ala Cys Asn Glu Phe Leu Ala Arg Asn Tyr Pro Thr Val 1985 1990 1995Ser Ser Tyr Gln Ile Thr Asp Glu Tyr Asp Ala Tyr Leu Asp Met 2000 2005 2010Val Asp Gly Ser Glu Ser Cys Leu Asp Arg Ala Thr Phe Asn Pro 2015 2020 2025Ser Lys Leu Arg Ser Tyr Pro Lys Gln His Ala Tyr His Ala Pro 2030 2035 2040Ser Ile Arg Ser Ala Val Pro Ser Pro Phe Gln Asn Thr Leu Gln 2045 2050 2055Asn Val Leu Ala Ala Ala Thr Lys Arg Asn Cys Asn Val Thr Gln 2060 2065 2070Met Arg Glu Leu Pro Thr Leu Asp Ser Ala Val Phe Asn Val Glu 2075 2080 2085Cys Phe Lys Lys Phe Ala Cys Asn Gln Glu Tyr Trp Glu Glu Phe 2090 2095 2100Ala Ala Ser Pro Ile Arg Ile Thr Thr Glu Asn Leu Ala Thr Tyr 2105 2110 2115Val Thr Lys Leu Lys Gly Pro Lys Ala Ala Ala Leu Phe Ala Lys 2120 2125 2130Thr His Asn Leu Leu Pro Leu Gln Glu Val Pro Met Asp Arg Phe 2135 2140 2145Thr Val Asp Met Lys Arg Asp Val Lys Val Thr Pro Gly Thr Lys 2150 2155 2160His Thr Glu Glu Arg Pro Lys Val Gln Val Ile Gln Ala Ala Glu 2165 2170 2175Pro Leu Ala Thr Ala Tyr Leu Cys Gly Ile His Arg Glu Leu Val 2180 2185 2190Arg Arg Leu Asn Ala Val Leu Leu Pro Asn Val His Thr Leu Phe 2195 2200 2205Asp Met Ser Ala Glu Asp Phe Asp Ala Ile Ile Ala Ala His Phe 2210 2215 2220Lys Pro Gly Asp Thr Val Leu Glu Thr Asp Ile Ala Ser Phe Asp 2225 2230 2235Lys Ser Gln Asp Asp Ser Leu Ala Leu Thr Ala Leu Met Leu Leu 2240 2245 2250Glu Asp Leu Gly Val Asp His Ser Leu Leu Asp Leu Ile Glu Ala 2255 2260 2265Ala Phe Gly Glu Ile Ser Ser Cys His Leu Pro Thr Gly Thr Arg 2270 2275 2280Phe Lys Phe Gly Ala Met Met Lys Ser Gly Met Phe Leu Thr Leu 2285 2290 2295Phe Val Asn Thr Leu Leu Asn Ile Thr Ile Ala Ser Arg Val Leu 2300 2305 2310Glu Asp Arg Leu Thr Lys Ser Ala Cys Ala Ala Phe Ile Gly Asp 2315 2320 2325Asp Asn Ile Ile His Gly Val Val Ser Asp Glu Leu Met Ala Ala 2330 2335 2340Arg Cys Ala Thr Trp Met Asn Met Glu Val Lys Ile Ile Asp Ala 2345 2350 2355Val Val Ser Leu Lys Ala Pro Tyr Phe Cys Gly Gly Phe Ile Leu 2360 2365 2370His Asp Thr Val Thr Gly Thr Ala Cys Arg Val Ala Asp Pro Leu 2375 2380 2385Lys Arg Leu Phe Lys Leu Gly Lys Pro Leu Ala Ala Gly Asp Glu 2390 2395 2400Gln Asp Glu Asp Arg Arg Arg Ala Leu Ala Asp Glu Val Ile Arg 2405 2410 2415Trp Gln Arg Thr Gly Leu Ile Asp Glu Leu Glu Lys Ala Val Tyr 2420 2425 2430Ser Arg Tyr Glu Val Gln Gly Ile Ser Val Val Val Met Ser Met 2435 2440 2445Ala Thr Phe Ala Ser Ser Arg Ser Asn Phe Glu Lys Leu Arg Gly 2450 2455 2460Pro Val Ile Thr Leu Tyr Gly Gly Pro Lys 2465 2470332473PRTChikungunya virus 33Met Asp Pro Val Tyr Val Asp Ile Asp Ala Asp Ser Ala Phe Leu Lys1 5 10 15Ala Leu Gln Arg Ala Tyr Pro Met Phe Glu Val Glu Pro Arg Gln Val 20 25 30Thr Pro Asn Asp His Ala Asn Ala Arg Ala Phe Ser His Leu Ala Ile 35 40 45Lys Leu Ile Glu Gln Glu Ile Asp Pro Asp Ser Thr Ile Leu Asp Ile 50 55 60Gly Ser Ala Pro Ala Arg Arg Met Met Ser Asp Arg Lys Tyr His Cys65 70 75 80Val Cys Pro Met Arg Ser Ala Glu Asp Pro Glu Arg Leu Ala Asn Tyr 85 90 95Ala Arg Lys Leu Ala Ser Ala Ala Gly Lys Val Leu Asp Arg Asn Ile 100 105 110Ser Gly Lys Ile Gly Asp Leu Gln Ala Val Met Ala Val Pro Asp Thr 115 120 125Glu Thr Pro Thr Phe Cys Leu His Thr Asp Val Ser Cys Arg Gln Arg 130 135 140Ala Asp Val Ala Ile Tyr Gln Asp Val Tyr Ala Val His Ala Pro Thr145 150 155 160Ser Leu Tyr His Gln Ala Ile Lys Gly Val Arg Val Ala Tyr Trp Val 165 170 175Gly Phe Asp Thr Thr Pro Phe Met Tyr Asn Ala Met Ala Gly Ala Tyr 180 185 190Pro Ser Tyr Ser Thr Asn Trp Ala Asp Glu Gln Val Leu Lys Ala Lys 195 200 205Asn Ile Gly Leu Cys Ser Thr Asp Leu Thr Glu Gly Arg Arg Gly Lys 210 215 220Leu Ser Ile Met Arg Gly Lys Lys Leu Lys Pro Cys Asp Arg Val Leu225 230 235 240Phe Ser Val Gly Ser Thr Leu Tyr Pro Glu Ser Arg Lys Leu Leu Lys 245 250 255Ser Trp His Leu Pro Ser Val Phe His Leu Lys Gly Lys Leu Ser Phe 260 265 270Thr Cys Arg Cys Asp Thr Val Val Ser Cys Glu Gly Tyr Val Val Lys 275 280 285Arg Ile Thr Met Ser Pro Gly Leu Tyr Gly Lys Thr Thr Gly Tyr Ala 290 295 300Val Thr His His Ala Asp Gly Phe Leu Met Cys Lys Thr Thr Asp Thr305 310 315 320Val Asp Gly Glu Arg Val Ser Phe Ser Val Cys Thr Tyr Val Pro Ala 325 330 335Thr Ile Cys Asp Gln Met Thr Gly Ile Leu Ala Thr Glu Val Thr Pro 340 345 350Glu Asp Ala Gln Lys Leu Leu Val Gly Leu Asn Gln Arg Ile Val Val 355 360 365Asn Gly Arg Thr Gln Arg Asn Thr Asn Thr Met Lys Asn Tyr Leu Leu 370 375 380Pro Val Val Ala Gln Ala Phe Ser Lys Trp Ala Lys Glu Cys Arg Lys385 390 395 400Asp Met Glu Asp Glu Lys Leu Leu Gly Val Arg Glu Arg Thr Leu Thr 405 410 415Cys Cys Cys Leu Trp Ala Phe Lys Lys Gln Lys Thr His Thr Val Tyr 420 425 430Lys Arg Pro Asp Thr Gln Ser Ile Gln Lys Val Gln Ala Glu Phe Asp 435 440 445Ser Phe Val Val Pro Ser Leu Trp Ser Ser Gly Leu Ser Ile Pro Leu 450 455 460Arg Thr Arg Ile Lys Trp Leu Leu Ser Lys Val Pro Lys Thr Asp Leu465 470 475 480Ile Pro Tyr Ser Gly Asp Ala Arg Glu Ala Arg Asp Ala Glu Lys Glu 485 490 495Ala Glu Glu Glu Arg Glu Ala Glu Leu Thr Arg Glu Ala Leu Pro Pro 500 505 510Leu Gln Ala Ala Gln Glu Asp Val Gln Val Glu Ile Asp Val Glu Gln 515 520 525Leu Glu Asp Arg Ala Gly Ala Gly Ile Ile Glu Thr Pro Arg Gly Ala 530 535 540Ile Lys Val Thr Ala Gln Pro Thr Asp His Val Val Gly Glu Tyr Leu545 550 555 560Val Leu Ser Pro Gln Thr Val Leu Arg Ser Gln Lys Leu Ser Leu Ile 565 570 575His Ala Leu Ala Glu Gln Val Lys Thr Cys Thr His Asn Gly Arg Ala 580 585 590Gly Arg Tyr Ala Val Glu Ala Tyr Asp Gly Arg Val Leu Val Pro Ser 595 600 605Gly Tyr Ala Ile Ser Pro Glu Asp Phe Gln Ser Leu Ser Glu Ser Ala 610 615 620Thr Met Val Tyr Asn Glu Arg Glu Phe Val Asn Arg Lys Leu His His625 630 635 640Ile Ala Met His Gly Pro Ala Leu Asn Thr Asp Glu Glu Ser Tyr Glu 645 650 655Leu Val Arg Ala Glu Arg Thr Glu His Glu Tyr Val Tyr Asp Val Asp 660 665 670Gln Arg Arg Cys Cys Lys Lys Glu Glu Ala Ala Gly Leu Val Leu Val 675 680 685Gly Asp Leu Thr Asn Pro Pro Tyr His Glu Phe Ala Tyr Glu Gly Leu 690 695 700Lys Ile Arg Pro Ala Cys Pro Tyr Lys Ile Ala Val Ile Gly Val Phe705 710 715 720Gly Val Pro Gly Ser Gly Lys Ser Ala Ile Ile Lys Asn Leu Val Thr 725 730 735Arg Gln Asp Leu Val Thr Ser Gly Lys Lys Glu Asn Cys Gln Glu Ile 740 745 750Thr Thr Asp Val Met Arg Gln Arg Gly Leu Glu Ile Ser Ala Arg Thr 755 760 765Val Asp Ser Leu Leu Leu Asn Gly Cys Asn Arg Pro Val Asp Val Leu 770 775 780Tyr Val Asp Glu Ala Phe Ala Cys His Ser Gly Thr Leu Leu Ala Leu785 790 795 800Ile Ala Leu Val Arg Pro Arg Gln Lys Val Val Leu Cys Gly Asp Pro 805 810 815Lys Gln Cys Gly Phe Phe Asn Met Met Gln Met Lys Val Asn Tyr Asn 820 825 830His Asn Ile Cys Thr Gln Val Tyr His Lys Ser Ile Ser Arg Arg Cys 835 840 845Thr Leu Pro Val Thr Ala Ile Val Ser Ser Leu His Tyr Glu Gly Lys 850 855 860Met Arg Thr Thr Asn Glu Tyr Asn Lys Pro Ile Val Val Asp Thr Thr865 870 875 880Gly Ser Thr Lys Pro Asp Pro Gly Asp Leu Val Leu Thr Cys Phe Arg 885 890 895Gly Trp Val Lys Gln Leu Gln Ile Asp Tyr Arg Gly Tyr Glu Val Met 900 905 910Thr Ala Ala Ala Ser Gln Gly Leu Thr Arg Lys Gly Val Tyr Ala Val 915 920 925Arg Gln Lys Val Asn Glu Asn Pro Leu Tyr Ala Ser Thr Ser Glu His 930 935 940Val Asn Val Leu Leu Thr Arg Thr Glu Gly Lys Leu Val Trp Lys Thr945 950 955 960Leu Ser Gly Asp Pro Trp Ile Lys Thr Leu Gln Asn Pro Pro Lys Gly 965 970 975Asn Phe Lys Ala Thr Ile Lys Glu Trp Glu Val Glu His Ala Ser Ile 980 985 990Met Ala Gly Ile Cys Ser His Gln Met Thr Phe Asp Thr Phe Gln Asn 995 1000 1005Lys Ala Asn Val Cys Trp Ala Lys Ser Leu Val Pro Ile Leu Glu 1010 1015 1020Thr Ala Gly Ile Lys Leu Asn Asp Arg Gln Trp Ser Gln Ile Ile 1025 1030 1035Gln Ala Phe Lys Glu Asp Lys Ala Tyr Ser Pro Glu Val Ala Leu 1040

1045 1050Asn Glu Ile Cys Thr Arg Met Tyr Gly Val Asp Leu Asp Ser Gly 1055 1060 1065Leu Phe Ser Lys Pro Leu Val Ser Val Tyr Tyr Ala Asp Asn His 1070 1075 1080Trp Asp Asn Arg Pro Gly Gly Lys Met Phe Gly Phe Asn Pro Glu 1085 1090 1095Ala Ala Ser Ile Leu Glu Arg Lys Tyr Pro Phe Thr Lys Gly Lys 1100 1105 1110Trp Asn Ile Asn Lys Gln Ile Cys Val Thr Thr Arg Arg Ile Glu 1115 1120 1125Asp Phe Asn Pro Thr Thr Asn Ile Ile Pro Ala Asn Arg Arg Leu 1130 1135 1140Pro His Ser Leu Val Ala Glu His Arg Pro Val Lys Gly Glu Arg 1145 1150 1155Met Glu Trp Leu Val Asn Lys Ile Asn Gly His His Val Leu Leu 1160 1165 1170Val Ser Gly Tyr Asn Leu Ala Leu Pro Thr Lys Arg Val Thr Trp 1175 1180 1185Val Ala Pro Leu Gly Val Arg Gly Ala Asp Tyr Thr Tyr Asn Leu 1190 1195 1200Glu Leu Gly Leu Pro Ala Thr Leu Gly Arg Tyr Asp Leu Val Val 1205 1210 1215Ile Asn Ile His Thr Pro Phe Arg Ile His His Tyr Gln Gln Cys 1220 1225 1230Val Asp His Ala Met Lys Leu Gln Met Leu Gly Gly Asp Ser Leu 1235 1240 1245Arg Leu Leu Lys Pro Gly Gly Ser Leu Leu Ile Arg Ala Tyr Gly 1250 1255 1260Tyr Ala Asp Arg Thr Ser Glu Arg Val Ile Cys Val Leu Gly Arg 1265 1270 1275Lys Phe Arg Ser Ser Arg Ala Leu Lys Pro Pro Cys Val Thr Ser 1280 1285 1290Asn Thr Glu Met Phe Phe Leu Phe Ser Asn Phe Asp Asn Gly Arg 1295 1300 1305Arg Asn Phe Thr Thr His Val Met Asn Asn Gln Leu Asn Ala Ala 1310 1315 1320Phe Val Gly Gln Val Thr Arg Ala Gly Cys Ala Pro Ser Tyr Arg 1325 1330 1335Val Lys Arg Met Asp Ile Ala Lys Asn Asp Glu Glu Cys Val Val 1340 1345 1350Asn Ala Ala Asn Pro Arg Gly Leu Pro Gly Asp Gly Val Cys Lys 1355 1360 1365Ala Val Tyr Lys Lys Trp Pro Glu Ser Phe Lys Asn Ser Ala Thr 1370 1375 1380Pro Val Gly Thr Ala Lys Thr Val Met Cys Gly Thr Tyr Pro Val 1385 1390 1395Ile His Ala Val Gly Pro Asn Phe Ser Asn Tyr Ser Glu Ser Glu 1400 1405 1410Gly Asp Arg Glu Leu Ala Ala Ala Tyr Arg Glu Val Ala Lys Glu 1415 1420 1425Val Thr Arg Leu Gly Val Asn Ser Val Ala Ile Pro Leu Leu Ser 1430 1435 1440Thr Gly Val Tyr Ser Gly Gly Lys Asp Arg Leu Thr Gln Ser Leu 1445 1450 1455Asn His Leu Phe Thr Ala Met Asp Ser Thr Asp Ala Asp Val Val 1460 1465 1470Ile Tyr Cys Arg Asp Lys Glu Trp Glu Lys Lys Ile Ser Glu Ala 1475 1480 1485Ile Gln Met Arg Thr Gln Val Glu Leu Leu Asp Glu His Ile Ser 1490 1495 1500Ile Asp Cys Asp Ile Val Arg Val His Pro Asp Ser Ser Leu Ala 1505 1510 1515Gly Arg Lys Gly Tyr Ser Thr Thr Glu Gly Ala Leu Tyr Ser Tyr 1520 1525 1530Leu Glu Gly Thr Arg Phe His Gln Thr Ala Val Asp Met Ala Glu 1535 1540 1545Ile His Thr Met Trp Pro Lys Gln Thr Glu Ala Asn Glu Gln Val 1550 1555 1560Cys Leu Tyr Ala Leu Gly Glu Ser Ile Glu Ser Ile Arg Gln Lys 1565 1570 1575Cys Pro Val Asp Asp Ala Asp Ala Ser Ser Pro Pro Lys Thr Val 1580 1585 1590Pro Cys Leu Cys Arg Tyr Ala Met Thr Pro Glu Arg Val Thr Arg 1595 1600 1605Leu Arg Met Asn His Val Thr Ser Ile Ile Val Cys Ser Ser Phe 1610 1615 1620Pro Leu Pro Lys Tyr Lys Ile Glu Gly Val Gln Lys Val Lys Cys 1625 1630 1635Ser Lys Val Met Leu Phe Asp His Asn Val Pro Ser Arg Val Ser 1640 1645 1650Pro Arg Glu Tyr Arg Ser Ser Gln Glu Ser Ala Gln Glu Ala Ser 1655 1660 1665Thr Ile Thr Ser Leu Thr His Ser Gln Phe Asp Leu Ser Val Asp 1670 1675 1680Gly Glu Ile Leu Pro Val Pro Ser Asp Leu Asp Ala Asp Ala Pro 1685 1690 1695Ala Leu Glu Pro Ala Leu Asp Asp Gly Ala Thr His Thr Leu Pro 1700 1705 1710Ser Thr Thr Gly Asn Leu Ala Ala Val Ser Asp Trp Val Met Ser 1715 1720 1725Thr Val Pro Val Ala Pro Pro Arg Arg Arg Arg Gly Arg Asn Leu 1730 1735 1740Thr Val Thr Cys Asp Glu Arg Glu Gly Asn Ile Thr Pro Met Ala 1745 1750 1755Ser Val Arg Phe Phe Arg Ala Glu Leu Cys Pro Val Val Gln Glu 1760 1765 1770Thr Ala Glu Thr Arg Asp Thr Ala Met Ser Leu Gln Ala Pro Pro 1775 1780 1785Ser Thr Ala Thr Glu Pro Asn His Pro Pro Ile Ser Phe Gly Ala 1790 1795 1800Ser Ser Glu Thr Phe Pro Ile Thr Phe Gly Asp Phe Asn Glu Gly 1805 1810 1815Glu Ile Glu Ser Leu Ser Ser Glu Leu Leu Thr Phe Gly Asp Phe 1820 1825 1830Leu Pro Gly Glu Val Asp Asp Leu Thr Asp Ser Asp Trp Ser Thr 1835 1840 1845Cys Ser Asp Thr Asp Asp Glu Leu Leu Asp Arg Ala Gly Gly Tyr 1850 1855 1860Ile Phe Ser Ser Asp Thr Gly Pro Gly His Leu Gln Gln Lys Ser 1865 1870 1875Val Arg Gln Ser Val Leu Pro Val Asn Thr Leu Glu Glu Val His 1880 1885 1890Glu Glu Lys Cys Tyr Pro Pro Lys Leu Asp Glu Ala Lys Glu Gln 1895 1900 1905Leu Leu Leu Lys Lys Leu Gln Glu Ser Ala Ser Met Ala Asn Arg 1910 1915 1920Ser Arg Tyr Gln Ser Arg Lys Val Glu Asn Met Lys Ala Ala Ile 1925 1930 1935Ile Gln Arg Leu Lys Arg Gly Cys Arg Leu Tyr Leu Met Ser Glu 1940 1945 1950Thr Pro Lys Val Pro Thr Tyr Arg Thr Thr Tyr Pro Ala Pro Val 1955 1960 1965Tyr Ser Pro Pro Ile Asn Val Arg Leu Ser Asn Pro Glu Ser Ala 1970 1975 1980Val Ala Ala Cys Asn Glu Phe Leu Ala Arg Asn Tyr Pro Thr Val 1985 1990 1995Ser Ser Tyr Gln Ile Thr Asp Glu Tyr Asp Ala Tyr Leu Asp Met 2000 2005 2010Val Asp Gly Ser Glu Ser Cys Leu Asp Arg Ala Thr Phe Asn Pro 2015 2020 2025Ser Lys Leu Arg Ser Tyr Pro Lys Gln His Ala Tyr His Ala Pro 2030 2035 2040Ser Ile Arg Ser Ala Val Pro Ser Pro Phe Gln Asn Thr Leu Gln 2045 2050 2055Asn Val Leu Ala Ala Ala Thr Lys Arg Asn Cys Asn Val Thr Gln 2060 2065 2070Met Arg Glu Leu Pro Thr Leu Asp Ser Ala Val Phe Asn Val Glu 2075 2080 2085Cys Phe Lys Lys Phe Ala Cys Asn Gln Glu Tyr Trp Glu Glu Phe 2090 2095 2100Ala Ala Ser Pro Ile Arg Ile Thr Thr Glu Asn Leu Ala Thr Tyr 2105 2110 2115Val Thr Lys Leu Lys Gly Pro Lys Ala Ala Ala Leu Phe Ala Lys 2120 2125 2130Thr His Asn Leu Leu Pro Leu Gln Glu Val Pro Met Asp Arg Phe 2135 2140 2145Thr Val Asp Met Lys Arg Asp Val Lys Val Thr Pro Gly Thr Lys 2150 2155 2160His Thr Glu Glu Arg Pro Lys Val Gln Val Ile Gln Ala Ala Glu 2165 2170 2175Pro Leu Ala Thr Ala Tyr Leu Cys Gly Ile His Arg Glu Leu Val 2180 2185 2190Arg Arg Leu Asn Ala Val Leu Leu Pro Asn Val His Thr Leu Phe 2195 2200 2205Asp Met Ser Ala Glu Asp Phe Asp Ala Ile Ile Ala Ala His Phe 2210 2215 2220Lys Pro Gly Asp Thr Val Leu Glu Thr Asp Ile Ala Ser Phe Asp 2225 2230 2235Lys Ser Gln Asp Asp Ser Leu Ala Leu Thr Ala Leu Met Leu Leu 2240 2245 2250Glu Asp Leu Gly Val Asp His Ser Leu Leu Asp Leu Ile Glu Ala 2255 2260 2265Ala Phe Gly Glu Ile Ser Ser Cys His Leu Pro Thr Gly Thr Arg 2270 2275 2280Phe Lys Phe Gly Ala Met Met Lys Ser Gly Met Phe Leu Thr Leu 2285 2290 2295Phe Val Asn Thr Leu Leu Asn Ile Thr Ile Ala Ser Arg Val Leu 2300 2305 2310Glu Asp Arg Leu Thr Lys Ser Ala Cys Ala Ala Phe Ile Gly Asp 2315 2320 2325Asp Asn Ile Ile His Gly Val Val Ser Asp Glu Leu Met Ala Ala 2330 2335 2340Arg Cys Ala Thr Trp Met Asn Met Glu Val Lys Ile Ile Asp Ala 2345 2350 2355Val Val Ser Leu Lys Ala Pro Tyr Phe Cys Gly Gly Phe Ile Leu 2360 2365 2370His Asp Thr Val Thr Gly Thr Ala Cys Arg Val Ala Asp Pro Leu 2375 2380 2385Lys Arg Leu Phe Lys Leu Gly Lys Pro Leu Ala Ala Gly Asp Glu 2390 2395 2400Gln Asp Glu Asp Arg Arg Arg Ala Leu Ala Asp Glu Val Ile Arg 2405 2410 2415Trp Gln Arg Thr Gly Leu Ile Asp Glu Leu Glu Lys Ala Val Tyr 2420 2425 2430Ser Arg Tyr Glu Val Gln Gly Ile Ser Val Val Val Met Ser Met 2435 2440 2445Ala Thr Phe Ala Ser Ser Arg Ser Asn Phe Glu Lys Leu Arg Gly 2450 2455 2460Pro Val Ile Thr Leu Tyr Gly Gly Pro Lys 2465 2470342472PRTChikungunya virus 34Met Asp Pro Val Tyr Val Asp Ile Asp Ala Asp Ser Ala Phe Leu Lys1 5 10 15Ala Leu Gln Arg Ala Tyr Pro Met Phe Glu Val Glu Pro Arg Gln Val 20 25 30Thr Pro Asn Asp His Ala Asn Ala Arg Ala Phe Ser His Leu Ala Ile 35 40 45Lys Leu Ile Glu Gln Glu Ile Asp Pro Asp Ser Thr Ile Leu Asp Ile 50 55 60Gly Ser Ala Pro Ala Arg Arg Met Met Ser Asp Arg Lys Tyr His Cys65 70 75 80Val Cys Pro Met Arg Ser Ala Glu Asp Pro Glu Arg Leu Ala Asn Tyr 85 90 95Ala Arg Lys Leu Ala Ser Ala Ala Gly Lys Val Leu Asp Arg Asn Ile 100 105 110Ser Gly Lys Ile Gly Asp Leu Gln Ala Val Met Ala Val Pro Asp Thr 115 120 125Glu Thr Pro Thr Phe Cys Leu His Thr Asp Val Ser Cys Arg Gln Arg 130 135 140Ala Asp Val Ala Ile Tyr Gln Asp Val Tyr Ala Val His Ala Pro Thr145 150 155 160Ser Leu Tyr His Gln Ala Ile Lys Gly Val Arg Val Ala Tyr Trp Val 165 170 175Gly Phe Asp Thr Thr Pro Phe Met Tyr Asn Ala Met Ala Gly Ala Tyr 180 185 190Pro Ser Tyr Ser Thr Asn Trp Ala Asp Glu Gln Val Leu Lys Ala Lys 195 200 205Asn Ile Gly Leu Cys Ser Thr Asp Leu Thr Glu Gly Arg Arg Gly Lys 210 215 220Leu Ser Ile Met Arg Gly Lys Lys Leu Lys Pro Cys Asp Arg Val Leu225 230 235 240Phe Ser Val Gly Ser Thr Leu Tyr Pro Glu Ser Arg Lys Leu Leu Lys 245 250 255Ser Trp His Leu Pro Ser Val Phe His Leu Lys Gly Lys Leu Ser Phe 260 265 270Thr Cys Arg Cys Asp Thr Val Val Ser Cys Glu Gly Tyr Val Val Lys 275 280 285Arg Ile Thr Met Ser Pro Gly Leu Tyr Gly Lys Thr Ile Gly Tyr Ala 290 295 300Val Thr His His Ala Asp Gly Phe Leu Met Cys Lys Thr Thr Asp Thr305 310 315 320Val Asp Gly Glu Arg Val Ser Phe Ser Val Cys Thr Tyr Val Pro Ala 325 330 335Thr Ile Cys Asp Gln Met Thr Gly Ile Leu Ala Thr Glu Val Thr Pro 340 345 350Glu Asp Ala Gln Lys Leu Leu Val Gly Leu Asn Gln Arg Ile Val Val 355 360 365Asn Gly Arg Thr Gln Arg Asn Thr Asn Thr Met Lys Asn Tyr Leu Leu 370 375 380Pro Val Val Ala Gln Ala Phe Ser Lys Trp Ala Lys Glu Cys Arg Lys385 390 395 400Asp Met Glu Asp Glu Lys Leu Leu Gly Val Arg Glu Arg Thr Leu Thr 405 410 415Cys Cys Cys Leu Trp Ala Phe Lys Lys Gln Lys Thr His Thr Val Tyr 420 425 430Lys Arg Pro Asp Thr Gln Ser Ile Gln Lys Val Gln Ala Glu Phe Asp 435 440 445Ser Phe Val Val Pro Ser Leu Trp Ser Ser Gly Leu Ser Ile Pro Leu 450 455 460Arg Thr Arg Ile Lys Trp Leu Leu Ser Lys Val Pro Lys Thr Asp Leu465 470 475 480Ile Pro Tyr Ser Gly Asp Ala Arg Glu Ala Arg Asp Ala Glu Lys Glu 485 490 495Ala Glu Glu Glu Arg Glu Ala Glu Leu Thr Arg Glu Ala Leu Pro Pro 500 505 510Leu Gln Ala Ala Gln Glu Asp Val Gln Val Glu Ile Asp Val Glu Gln 515 520 525Leu Glu Asp Arg Ala Gly Ala Gly Ile Ile Glu Thr Pro Arg Gly Ala 530 535 540Ile Lys Val Thr Ala Gln Pro Thr Asp His Val Val Gly Glu Tyr Leu545 550 555 560Val Leu Ser Pro Gln Thr Val Leu Arg Ser Gln Lys Leu Ser Leu Ile 565 570 575His Ala Leu Ala Glu Gln Val Lys Thr Cys Thr His Asn Gly Arg Ala 580 585 590Gly Arg Tyr Ala Val Glu Ala Tyr Asp Gly Arg Val Leu Val Pro Ser 595 600 605Gly Tyr Ala Ile Ser Pro Glu Asp Phe Gln Ser Leu Ser Glu Ser Ala 610 615 620Thr Met Val Tyr Asn Glu Arg Glu Phe Val Asn Arg Lys Leu His His625 630 635 640Ile Ala Met His Gly Pro Ala Leu Asn Thr Asp Glu Glu Ser Tyr Glu 645 650 655Leu Val Arg Ala Glu Arg Thr Glu His Glu Tyr Val Tyr Asp Val Asp 660 665 670Gln Arg Arg Cys Cys Lys Lys Glu Glu Ala Ala Gly Leu Val Leu Val 675 680 685Gly Asp Leu Thr Asn Pro Pro Tyr His Glu Phe Ala Tyr Glu Gly Leu 690 695 700Lys Ile Arg Pro Ala Cys Pro Tyr Lys Ile Ala Val Ile Gly Val Phe705 710 715 720Gly Val Pro Gly Ser Gly Lys Ser Ala Ile Ile Lys Asn Leu Val Thr 725 730 735Arg Gln Asp Leu Val Thr Ser Gly Lys Lys Glu Asn Cys Gln Glu Ile 740 745 750Thr Thr Asp Val Met Arg Gln Arg Gly Leu Glu Ile Ser Ala Arg Thr 755 760 765Val Asp Ser Leu Leu Leu Asn Gly Cys Asn Arg Pro Val Asp Val Leu 770 775 780Tyr Val Asp Glu Ala Phe Ala Cys His Ser Gly Thr Leu Leu Ala Leu785 790 795 800Ile Ala Leu Val Arg Pro Arg Gln Lys Val Val Leu Cys Gly Asp Pro 805 810 815Lys Gln Cys Gly Phe Phe Asn Met Met Gln Met Lys Val Asn Tyr Asn 820 825 830His Asn Ile Cys Thr Gln Val Tyr His Lys Ser Ile Ser Arg Arg Cys 835 840 845Thr Leu Pro Val Thr Ala Ile Val Ser Ser Leu His Tyr Glu Gly Lys 850 855 860Met Arg Thr Thr Asn Glu Tyr Asn Lys Pro Ile Val Val Asp Thr Thr865 870 875 880Gly Ser Thr Lys Pro Asp Pro Gly Asp Leu Val Leu Thr Cys Phe Arg 885 890 895Gly Trp Val Lys Gln Leu Gln Ile Asp Tyr Arg Gly Tyr Glu Val Met 900 905 910Thr Ala Ala Ala Ser Gln Gly Leu Thr Arg Lys Gly Val Tyr Ala Val 915 920 925Arg Gln Lys Val Asn Glu Asn Pro Leu Tyr Ala Ser Thr Ser Glu His 930 935 940Val Asn Val Leu Leu Thr Arg Thr Glu Gly Lys Leu Val Trp Lys Thr945 950 955 960Leu Ser Gly Asp Pro Trp Ile Lys Thr Leu Gln Asn Pro Pro Lys Gly 965 970 975Asn Phe Lys Ala Thr Ile Lys Glu Trp Glu Val Glu His Ala Ser Ile 980 985 990Met Ala Gly Ile Cys Ser His Gln Met Thr Phe Asp Thr Phe Gln Asn 995 1000 1005Lys Ala Asn Val Cys Trp Ala Lys Ser Leu Val Pro Ile Leu Glu 1010 1015

1020Thr Ala Gly Ile Lys Leu Asn Asp Arg Gln Trp Ser Gln Ile Ile 1025 1030 1035Gln Ala Phe Lys Glu Asp Lys Ala Tyr Ser Pro Glu Val Ala Leu 1040 1045 1050Asn Glu Ile Cys Thr Arg Met Tyr Gly Val Asp Leu Asp Ser Gly 1055 1060 1065Leu Phe Ser Lys Pro Leu Val Ser Val Tyr Tyr Ala Asp Asn His 1070 1075 1080Trp Asp Asn Arg Pro Gly Gly Lys Met Phe Gly Phe Asn Pro Glu 1085 1090 1095Ala Ala Ser Ile Leu Glu Arg Lys Tyr Pro Phe Thr Lys Gly Lys 1100 1105 1110Trp Asn Ile Asn Lys Gln Ile Cys Val Thr Thr Arg Arg Ile Glu 1115 1120 1125Asp Phe Asn Pro Thr Thr Asn Ile Ile Pro Ala Asn Arg Arg Leu 1130 1135 1140Pro His Ser Leu Val Ala Glu His Arg Pro Val Lys Gly Glu Arg 1145 1150 1155Met Glu Trp Leu Val Asn Lys Ile Asn Gly His His Val Leu Leu 1160 1165 1170Val Ser Gly Asn Asn Leu Ala Leu Pro Thr Lys Arg Val Thr Trp 1175 1180 1185Val Ala Pro Leu Gly Val Arg Gly Ala Asp Tyr Thr Tyr Asn Leu 1190 1195 1200Glu Leu Gly Leu Pro Ala Thr Leu Gly Arg Tyr Asp Leu Val Val 1205 1210 1215Ile Asn Ile His Thr Pro Phe Arg Ile His His Tyr Gln Gln Cys 1220 1225 1230Val Asp His Ala Met Lys Leu Gln Met Leu Gly Gly Asp Ser Leu 1235 1240 1245Arg Leu Leu Lys Pro Gly Gly Ser Leu Leu Ile Arg Ala Tyr Gly 1250 1255 1260Tyr Ala Asp Arg Thr Ser Glu Arg Val Ile Cys Val Leu Gly Arg 1265 1270 1275Lys Phe Arg Ser Ser Arg Ala Leu Lys Pro Pro Cys Val Thr Ser 1280 1285 1290Asn Thr Glu Met Phe Phe Leu Phe Ser Asn Phe Asp Asn Gly Arg 1295 1300 1305Arg Asn Phe Thr Thr His Val Met Asn Asn Gln Leu Asn Ala Ala 1310 1315 1320Phe Val Gly Gln Val Thr Arg Ala Gly Cys Ala Pro Ser Tyr Arg 1325 1330 1335Val Lys Arg Met Asp Ile Ala Lys Asn Asp Glu Glu Cys Val Val 1340 1345 1350Asn Ala Ala Asn Pro Arg Gly Leu Pro Gly Asp Gly Val Cys Lys 1355 1360 1365Ala Val Tyr Lys Lys Trp Pro Glu Ser Phe Lys Asn Ser Ala Thr 1370 1375 1380Pro Val Gly Thr Ala Lys Thr Val Met Cys Gly Thr Tyr Pro Val 1385 1390 1395Ile His Ala Val Gly Pro Asn Phe Ser Asn Tyr Ser Glu Ser Glu 1400 1405 1410Gly Asp Arg Glu Leu Ala Ala Ala Tyr Arg Glu Val Ala Lys Glu 1415 1420 1425Val Thr Arg Leu Gly Val Asn Ser Val Ala Ile Pro Leu Leu Ser 1430 1435 1440Thr Gly Val Tyr Ser Gly Gly Lys Asp Arg Leu Thr Gln Ser Leu 1445 1450 1455Asn His Leu Phe Thr Ala Met Asp Ser Thr Asp Ala Asp Val Val 1460 1465 1470Ile Tyr Cys Arg Asp Lys Glu Trp Glu Lys Lys Ile Ser Glu Ala 1475 1480 1485Ile Gln Met Arg Thr Gln Val Glu Leu Leu Asp Glu His Ile Ser 1490 1495 1500Ile Asp Cys Asp Ile Val Arg Val His Pro Asp Ser Ser Leu Ala 1505 1510 1515Gly Arg Lys Gly Tyr Ser Thr Thr Glu Gly Ala Leu Tyr Ser Tyr 1520 1525 1530Leu Glu Gly Thr Arg Phe His Gln Thr Ala Val Asp Met Ala Glu 1535 1540 1545Ile His Thr Met Trp Pro Lys Gln Thr Glu Ala Asn Glu Gln Val 1550 1555 1560Cys Leu Tyr Ala Leu Gly Glu Ser Ile Glu Ser Ile Arg Gln Lys 1565 1570 1575Cys Pro Val Asp Asp Ala Asp Ala Ser Ser Pro Pro Lys Thr Val 1580 1585 1590Pro Cys Leu Cys Arg Tyr Ala Met Thr Pro Glu Arg Val Thr Arg 1595 1600 1605Leu Arg Met Asn His Val Thr Ser Ile Ile Val Cys Ser Ser Phe 1610 1615 1620Pro Leu Pro Lys Tyr Lys Ile Glu Gly Val Gln Lys Val Lys Cys 1625 1630 1635Ser Lys Val Met Leu Phe Asp His Asn Val Pro Ser Arg Val Ser 1640 1645 1650Pro Arg Glu Tyr Arg Ser Ser Gln Glu Ser Ala Gln Glu Ala Ser 1655 1660 1665Thr Ile Thr Ser Leu Thr His Ser Gln Phe Asp Leu Ser Val Asp 1670 1675 1680Gly Glu Ile Leu Pro Val Pro Ser Asp Leu Asp Ala Asp Ala Pro 1685 1690 1695Ala Leu Glu Pro Ala Leu Asp Asp Gly Ala Thr His Thr Leu Pro 1700 1705 1710Ser Thr Thr Gly Asn Leu Ala Ala Val Ser Asp Trp Val Met Ser 1715 1720 1725Thr Val Pro Val Ala Pro Pro Arg Arg Arg Arg Gly Arg Asn Leu 1730 1735 1740Thr Val Thr Cys Asp Glu Arg Glu Gly Asn Ile Thr Pro Met Ala 1745 1750 1755Ser Val Arg Phe Phe Arg Ala Glu Leu Cys Pro Val Val Gln Glu 1760 1765 1770Thr Ala Glu Thr Arg Asp Thr Ala Met Ser Leu Gln Ala Pro Pro 1775 1780 1785Ser Thr Ala Thr Pro Asn His Pro Pro Ile Ser Phe Gly Ala Ser 1790 1795 1800Ser Glu Thr Phe Pro Ile Thr Phe Gly Asp Phe Asn Glu Gly Glu 1805 1810 1815Ile Glu Ser Leu Ser Ser Glu Leu Leu Thr Phe Gly Asp Phe Leu 1820 1825 1830Pro Gly Glu Val Asp Asp Leu Thr Asp Ser Asp Trp Ser Thr Cys 1835 1840 1845Ser Asp Thr Asp Asp Glu Leu Leu Asp Arg Ala Gly Gly Tyr Ile 1850 1855 1860Phe Ser Ser Asp Thr Gly Pro Gly His Leu Gln Gln Lys Ser Val 1865 1870 1875Arg Gln Ser Val Leu Pro Val Asn Thr Leu Glu Glu Val His Glu 1880 1885 1890Glu Lys Cys Tyr Pro Pro Lys Leu Asp Glu Ala Lys Glu Gln Leu 1895 1900 1905Leu Leu Lys Lys Leu Gln Glu Ser Ala Ser Met Ala Asn Arg Ser 1910 1915 1920Arg Tyr Gln Ser Arg Lys Val Glu Asn Met Lys Ala Ala Ile Ile 1925 1930 1935Gln Arg Leu Lys Arg Gly Cys Arg Leu Tyr Leu Met Ser Glu Thr 1940 1945 1950Pro Lys Val Pro Thr Tyr Arg Thr Thr Tyr Pro Ala Pro Val Tyr 1955 1960 1965Ser Pro Pro Ile Asn Val Arg Leu Ser Asn Pro Glu Ser Ala Val 1970 1975 1980Ala Ala Cys Asn Glu Phe Leu Ala Arg Asn Tyr Pro Thr Val Ser 1985 1990 1995Ser Tyr Gln Ile Thr Asp Glu Tyr Asp Ala Tyr Leu Asp Met Val 2000 2005 2010Asp Gly Ser Glu Ser Cys Leu Asp Arg Ala Thr Phe Asn Pro Ser 2015 2020 2025Lys Leu Arg Ser Tyr Pro Lys Gln His Ala Tyr His Ala Pro Ser 2030 2035 2040Ile Arg Ser Ala Val Pro Ser Pro Phe Gln Asn Thr Leu Gln Asn 2045 2050 2055Val Leu Ala Ala Ala Thr Lys Arg Asn Cys Asn Val Thr Gln Met 2060 2065 2070Arg Glu Leu Pro Thr Leu Asp Ser Ala Val Phe Asn Val Glu Cys 2075 2080 2085Phe Lys Lys Phe Ala Cys Asn Gln Glu Tyr Trp Glu Glu Phe Ala 2090 2095 2100Ala Ser Pro Ile Arg Ile Thr Thr Glu Asn Leu Ala Thr Tyr Val 2105 2110 2115Thr Lys Leu Lys Gly Pro Lys Ala Ala Ala Leu Phe Ala Lys Thr 2120 2125 2130His Asn Leu Leu Pro Leu Gln Glu Val Pro Met Asp Arg Phe Thr 2135 2140 2145Val Asp Met Lys Arg Asp Val Lys Val Thr Pro Gly Thr Lys His 2150 2155 2160Thr Glu Glu Arg Pro Lys Val Gln Val Ile Gln Ala Ala Glu Pro 2165 2170 2175Leu Ala Thr Ala Tyr Leu Cys Gly Ile His Arg Glu Leu Val Arg 2180 2185 2190Arg Leu Asn Ala Val Leu Leu Pro Asn Val His Thr Leu Phe Asp 2195 2200 2205Met Ser Ala Glu Asp Phe Asp Ala Ile Ile Ala Ala His Phe Lys 2210 2215 2220Pro Gly Asp Thr Val Leu Glu Thr Asp Ile Ala Ser Phe Asp Lys 2225 2230 2235Ser Gln Asp Asp Ser Leu Ala Leu Thr Ala Leu Met Leu Leu Glu 2240 2245 2250Asp Leu Gly Val Asp His Ser Leu Leu Asp Leu Ile Glu Ala Ala 2255 2260 2265Phe Gly Glu Ile Ser Ser Cys His Leu Pro Thr Gly Thr Arg Phe 2270 2275 2280Lys Phe Gly Ala Met Met Lys Ser Gly Met Phe Leu Thr Leu Phe 2285 2290 2295Val Asn Thr Leu Leu Asn Ile Thr Ile Ala Ser Arg Val Leu Glu 2300 2305 2310Asp Arg Leu Thr Lys Ser Ala Cys Ala Ala Phe Ile Gly Asp Asp 2315 2320 2325Asn Ile Ile His Gly Val Val Ser Asp Glu Leu Met Ala Ala Arg 2330 2335 2340Cys Ala Thr Trp Met Asn Met Glu Val Lys Ile Ile Asp Ala Val 2345 2350 2355Val Ser Leu Lys Ala Pro Tyr Phe Cys Gly Gly Phe Ile Leu His 2360 2365 2370Asp Thr Val Thr Gly Thr Ala Cys Arg Val Ala Asp Pro Leu Lys 2375 2380 2385Arg Leu Phe Lys Leu Gly Lys Pro Leu Ala Ala Gly Asp Glu Gln 2390 2395 2400Asp Glu Asp Arg Arg Arg Ala Leu Ala Asp Glu Val Ile Arg Trp 2405 2410 2415Gln Arg Thr Gly Leu Ile Asp Glu Leu Glu Lys Ala Val Tyr Ser 2420 2425 2430Arg Tyr Glu Val Gln Gly Ile Ser Val Val Val Met Ser Met Ala 2435 2440 2445Thr Phe Ala Ser Ser Arg Ser Asn Phe Glu Lys Leu Arg Gly Pro 2450 2455 2460Val Ile Thr Leu Tyr Gly Gly Pro Lys 2465 24703522DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 35cacgtagcct accagtttct ta 223621DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 36atggaacacc gatggtaggt g 213721DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 37aaccccgttc atgtacaatg c 213822DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 38cggtaccaca aagctgtcaa ac 223922DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 39cactgacctg ctgctgtcta tg 224021DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 40agtcctgcag cttcttcctt c 214122DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 41cgagtttgac agctttgtgg ta 224222DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 42atgactgcaa ttttgtatgg gc 224321DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 43caatctcgcc tgaagacttc c 214421DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 44tccactacaa tcggcttgtt g 214522DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 45gtgcggcttc ttcaatatga tg 224621DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 46tccaggccta ttatcccagt g 214722DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 47aacatctgca cccaagtgta cc 224822DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 48gtctcctgtt ggccggtata at 224922DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 49taataggcct ggagggaaga tg 225022DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 50ctacgcactc ttcatcgttc tt 225122DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 51gaacgagtca tctgcgtatt gg 225222DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 52atatctctgc catatccact gc 225322DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 53tctttacagc catggactcg ac 225422DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 54cgacaggtac ggtgctcatt ac 225522DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 55tgtacaggaa gcgagtacga cc 225622DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 56tctactttgc gcgactgata cc 225722DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 57acggacgacg agttacgact ag 225821DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 58cccagtattc ttggttgcat g 215920DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 59aaaacagcac gcttaccacg 206021DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 60aacttgaagc gcgtacctgt c 216121DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 61tcatagccgc acactttaag c 216221DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 62aggaccgccg tacaaagtta c 216321DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 63gcaggtgacg aacaagatga g 216419DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 64ccgcttaaag gccaatttg 196519DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 65tcgaagtcaa gcacgaagg 196622DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 66gtctgtcgct tcatttctga tg 226722DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 67tgcttgagga caacgtcatg ag 226819DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 68tttgtgattg gtgaccgcg 196922DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 69agtccggcaa cgtaaagatc ac 227021DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 70aaaggttgct gctcgttcca c 217122DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 71agttgtgtca gtggcctcgt tc 227222DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 72taaaggacgc ggagcttagc tg 227321DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 73acaaaaccgt catcccgtct c 217422DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 74tgactatgtg gtccttcgga gg 227521DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 75cagcaagaaa ggcaagtgtg c 217620DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 76tttgccaatt atggtattca 207717PRTChikungunya virus 77Met Leu Leu Ser Val Pro Leu Leu Leu Leu Gly Leu Leu Gly Leu Ala1 5 10 15Ala782450PRTChikungunya virus 78Met Phe Glu Val Glu Pro Arg Gln Val Thr Pro Asn Asp His Ala Asn1 5 10 15Ala Arg Ala Phe Ser His Leu Ala Ile Lys Leu Ile Glu Gln Glu Ile 20 25 30Asp Pro Asp Ser Thr Ile Leu Asp Ile Gly Ser Ala Pro Ala Arg Arg 35 40 45Met Met Ser Asp Arg Lys Tyr His Cys Val Cys Pro Met Arg Ser Ala 50 55 60Glu Asp Pro

Glu Arg Leu Ala Asn Tyr Ala Arg Lys Leu Ala Ser Ala65 70 75 80Ala Gly Lys Val Leu Asp Arg Asn Ile Ser Gly Lys Ile Gly Asp Leu 85 90 95Gln Ala Val Met Ala Val Pro Asp Thr Glu Thr Pro Thr Phe Cys Leu 100 105 110His Thr Asp Val Ser Cys Arg Gln Arg Ala Asp Val Ala Ile Tyr Gln 115 120 125Asp Val Tyr Ala Val His Ala Pro Thr Ser Leu Tyr His Gln Ala Ile 130 135 140Lys Gly Val Arg Val Ala Tyr Trp Val Gly Phe Asp Thr Thr Pro Phe145 150 155 160Met Tyr Asn Ala Met Ala Gly Ala Tyr Pro Ser Tyr Ser Thr Asn Trp 165 170 175Ala Asp Glu Gln Val Leu Lys Ala Lys Asn Ile Gly Leu Cys Ser Thr 180 185 190Asp Leu Thr Glu Gly Arg Arg Gly Lys Leu Ser Ile Met Arg Gly Lys 195 200 205Lys Leu Lys Pro Cys Asp Arg Val Leu Phe Ser Val Gly Ser Thr Leu 210 215 220Tyr Pro Glu Ser Arg Lys Leu Leu Lys Ser Trp His Leu Pro Ser Val225 230 235 240Phe His Leu Lys Gly Lys Leu Ser Phe Thr Cys Arg Cys Asp Thr Val 245 250 255Val Ser Cys Glu Gly Tyr Val Val Lys Arg Ile Thr Met Ser Pro Gly 260 265 270Leu Tyr Gly Lys Thr Thr Gly Tyr Ala Val Thr His His Ala Asp Gly 275 280 285Phe Leu Met Cys Lys Thr Thr Asp Thr Val Asp Gly Glu Arg Val Ser 290 295 300Phe Ser Val Cys Thr Tyr Val Pro Ala Thr Ile Cys Asp Gln Met Thr305 310 315 320Gly Ile Leu Ala Thr Glu Val Thr Pro Glu Asp Ala Gln Lys Leu Leu 325 330 335Val Gly Leu Asn Gln Arg Ile Val Val Asn Gly Arg Thr Gln Arg Asn 340 345 350Thr Asn Thr Met Lys Asn Tyr Leu Leu Pro Val Val Ala Gln Ala Phe 355 360 365Ser Lys Trp Ala Lys Glu Cys Arg Lys Asp Met Glu Asp Glu Lys Leu 370 375 380Leu Gly Val Arg Glu Arg Thr Leu Thr Cys Cys Cys Leu Trp Ala Phe385 390 395 400Lys Lys Gln Lys Thr His Thr Val Tyr Lys Arg Pro Asp Thr Gln Ser 405 410 415Ile Gln Lys Val Gln Ala Glu Phe Asp Ser Phe Val Val Pro Ser Leu 420 425 430Trp Ser Ser Gly Leu Ser Ile Pro Leu Arg Thr Arg Ile Lys Trp Leu 435 440 445Leu Ser Lys Val Pro Lys Thr Asp Leu Ile Pro Tyr Ser Gly Asp Ala 450 455 460Arg Glu Ala Arg Asp Ala Glu Lys Glu Ala Glu Glu Glu Arg Glu Ala465 470 475 480Glu Leu Thr Arg Glu Ala Leu Pro Pro Leu Gln Ala Ala Gln Glu Asp 485 490 495Val Gln Val Glu Ile Asp Val Glu Gln Leu Glu Asp Arg Ala Gly Ala 500 505 510Gly Ile Ile Glu Thr Pro Arg Gly Ala Ile Lys Val Thr Ala Gln Pro 515 520 525Thr Asp His Val Val Gly Glu Tyr Leu Val Leu Ser Pro Gln Thr Val 530 535 540Leu Arg Ser Gln Lys Leu Ser Leu Ile His Ala Leu Ala Glu Gln Val545 550 555 560Lys Thr Cys Thr His Asn Gly Arg Ala Gly Arg Tyr Ala Val Glu Ala 565 570 575Tyr Asp Gly Arg Val Leu Val Pro Ser Gly Tyr Ala Ile Ser Pro Glu 580 585 590Asp Phe Gln Ser Leu Ser Glu Ser Ala Thr Met Val Tyr Asn Glu Arg 595 600 605Glu Phe Val Asn Arg Lys Leu His His Ile Ala Met His Gly Pro Ala 610 615 620Leu Asn Thr Asp Glu Glu Ser Tyr Glu Leu Val Arg Ala Glu Arg Thr625 630 635 640Glu His Glu Tyr Val Tyr Asp Val Asp Gln Arg Arg Cys Cys Lys Lys 645 650 655Glu Glu Ala Ala Gly Leu Val Leu Val Gly Asp Leu Thr Asn Pro Pro 660 665 670Tyr His Glu Phe Ala Tyr Glu Gly Leu Lys Ile Arg Pro Ala Cys Pro 675 680 685Tyr Lys Ile Ala Val Ile Gly Val Phe Gly Val Pro Gly Ser Gly Lys 690 695 700Ser Ala Ile Ile Lys Asn Leu Val Thr Arg Gln Asp Leu Val Thr Ser705 710 715 720Gly Lys Lys Glu Asn Cys Gln Glu Ile Thr Thr Asp Val Met Arg Gln 725 730 735Arg Gly Leu Glu Ile Ser Ala Arg Thr Val Asp Ser Leu Leu Leu Asn 740 745 750Gly Cys Asn Arg Pro Val Asp Val Leu Tyr Val Asp Glu Ala Phe Ala 755 760 765Cys His Ser Gly Thr Leu Leu Ala Leu Ile Ala Leu Val Arg Pro Arg 770 775 780Gln Lys Val Val Leu Cys Gly Asp Pro Lys Gln Cys Gly Phe Phe Asn785 790 795 800Met Met Gln Met Lys Val Asn Tyr Asn His Asn Ile Cys Thr Gln Val 805 810 815Tyr His Lys Ser Ile Ser Arg Arg Cys Thr Leu Pro Val Thr Ala Ile 820 825 830Val Ser Ser Leu His Tyr Glu Gly Lys Met Arg Thr Thr Asn Glu Tyr 835 840 845Asn Lys Pro Ile Val Val Asp Thr Thr Gly Ser Thr Lys Pro Asp Pro 850 855 860Gly Asp Leu Val Leu Thr Cys Phe Arg Gly Trp Val Lys Gln Leu Gln865 870 875 880Ile Asp Tyr Arg Gly Tyr Glu Val Met Thr Ala Ala Ala Ser Gln Gly 885 890 895Leu Thr Arg Lys Gly Val Tyr Ala Val Arg Gln Lys Val Asn Glu Asn 900 905 910Pro Leu Tyr Ala Ser Thr Ser Glu His Val Asn Val Leu Leu Thr Arg 915 920 925Thr Glu Gly Lys Leu Val Trp Lys Thr Leu Ser Gly Asp Pro Trp Ile 930 935 940Lys Thr Leu Gln Asn Pro Pro Lys Gly Asn Phe Lys Ala Thr Ile Lys945 950 955 960Glu Trp Glu Val Glu His Ala Ser Ile Met Ala Gly Ile Cys Ser His 965 970 975Gln Met Thr Phe Asp Thr Phe Gln Asn Lys Ala Asn Val Cys Trp Ala 980 985 990Lys Ser Leu Val Pro Ile Leu Glu Thr Ala Gly Ile Lys Leu Asn Asp 995 1000 1005Arg Gln Trp Ser Gln Ile Ile Gln Ala Phe Lys Glu Asp Lys Ala 1010 1015 1020Tyr Ser Pro Glu Val Ala Leu Asn Glu Ile Cys Thr Arg Met Tyr 1025 1030 1035Gly Val Asp Leu Asp Ser Gly Leu Phe Ser Lys Pro Leu Val Ser 1040 1045 1050Val Tyr Tyr Ala Asp Asn His Trp Asp Asn Arg Pro Gly Gly Lys 1055 1060 1065Met Phe Gly Phe Asn Pro Glu Ala Ala Ser Ile Leu Glu Arg Lys 1070 1075 1080Tyr Pro Phe Thr Lys Gly Lys Trp Asn Ile Asn Lys Gln Ile Cys 1085 1090 1095Val Thr Thr Arg Arg Ile Glu Asp Phe Asn Pro Thr Thr Asn Ile 1100 1105 1110Ile Pro Ala Asn Arg Arg Leu Pro His Ser Leu Val Ala Glu His 1115 1120 1125Arg Pro Val Lys Gly Glu Arg Met Glu Trp Leu Val Asn Lys Ile 1130 1135 1140Asn Gly His His Val Leu Leu Val Ser Gly Tyr Asn Leu Ala Leu 1145 1150 1155Pro Thr Lys Arg Val Thr Trp Val Ala Pro Leu Gly Val Arg Gly 1160 1165 1170Ala Asp Tyr Thr Tyr Asn Leu Glu Leu Gly Leu Pro Ala Thr Leu 1175 1180 1185Gly Arg Tyr Asp Leu Val Val Ile Asn Ile His Thr Pro Phe Arg 1190 1195 1200Ile His His Tyr Gln Gln Cys Val Asp His Ala Met Lys Leu Gln 1205 1210 1215Met Leu Gly Gly Asp Ser Leu Arg Leu Leu Lys Pro Gly Gly Ser 1220 1225 1230Leu Leu Ile Arg Ala Tyr Gly Tyr Ala Asp Arg Thr Ser Glu Arg 1235 1240 1245Val Ile Cys Val Leu Gly Arg Lys Phe Arg Ser Ser Arg Ala Leu 1250 1255 1260Lys Pro Pro Cys Val Thr Ser Asn Thr Glu Met Phe Phe Leu Phe 1265 1270 1275Ser Asn Phe Asp Asn Gly Arg Arg Asn Phe Thr Thr His Val Met 1280 1285 1290Asn Asn Gln Leu Asn Ala Ala Phe Val Gly Gln Val Thr Arg Ala 1295 1300 1305Gly Cys Ala Pro Ser Tyr Arg Val Lys Arg Met Asp Ile Ala Lys 1310 1315 1320Asn Asp Glu Glu Cys Val Val Asn Ala Ala Asn Pro Arg Gly Leu 1325 1330 1335Pro Gly Asp Gly Val Cys Lys Ala Val Tyr Lys Lys Trp Pro Glu 1340 1345 1350Ser Phe Lys Asn Ser Ala Thr Pro Val Gly Thr Ala Lys Thr Val 1355 1360 1365Met Cys Gly Thr Tyr Pro Val Ile His Ala Val Gly Pro Asn Phe 1370 1375 1380Ser Asn Tyr Ser Glu Ser Glu Gly Asp Arg Glu Leu Ala Ala Ala 1385 1390 1395Tyr Arg Glu Val Ala Lys Glu Val Thr Arg Leu Gly Val Asn Ser 1400 1405 1410Val Ala Ile Pro Leu Leu Ser Thr Gly Val Tyr Ser Gly Gly Lys 1415 1420 1425Asp Arg Leu Thr Gln Ser Leu Asn His Leu Phe Thr Ala Met Asp 1430 1435 1440Ser Thr Asp Ala Asp Val Val Ile Tyr Cys Arg Asp Lys Glu Trp 1445 1450 1455Glu Lys Lys Ile Ser Glu Ala Ile Gln Met Arg Thr Gln Val Glu 1460 1465 1470Leu Leu Asp Glu His Ile Ser Ile Asp Cys Asp Ile Val Arg Val 1475 1480 1485His Pro Asp Ser Ser Leu Ala Gly Arg Lys Gly Tyr Ser Thr Thr 1490 1495 1500Glu Gly Ala Leu Tyr Ser Tyr Leu Glu Gly Thr Arg Phe His Gln 1505 1510 1515Thr Ala Val Asp Met Ala Glu Ile His Thr Met Trp Pro Lys Gln 1520 1525 1530Thr Glu Ala Asn Glu Gln Val Cys Leu Tyr Ala Leu Gly Glu Ser 1535 1540 1545Ile Glu Ser Ile Arg Gln Lys Cys Pro Val Asp Asp Ala Asp Ala 1550 1555 1560Ser Ser Pro Pro Lys Thr Val Pro Cys Leu Cys Arg Tyr Ala Met 1565 1570 1575Thr Pro Glu Arg Val Thr Arg Leu Arg Met Asn His Val Thr Ser 1580 1585 1590Ile Ile Val Cys Ser Ser Phe Pro Leu Pro Lys Tyr Lys Ile Glu 1595 1600 1605Gly Val Gln Lys Val Lys Cys Ser Lys Val Met Leu Phe Asp His 1610 1615 1620Asn Val Pro Ser Arg Val Ser Pro Arg Glu Tyr Arg Ser Ser Gln 1625 1630 1635Glu Ser Ala Gln Glu Ala Ser Thr Ile Thr Ser Leu Thr His Ser 1640 1645 1650Gln Phe Asp Leu Ser Val Asp Gly Glu Ile Leu Pro Val Pro Ser 1655 1660 1665Asp Leu Asp Ala Asp Ala Pro Ala Leu Glu Pro Ala Leu Asp Asp 1670 1675 1680Gly Ala Thr His Thr Leu Pro Ser Thr Thr Gly Asn Leu Ala Ala 1685 1690 1695Val Ser Asp Trp Val Met Ser Thr Val Pro Val Ala Pro Pro Arg 1700 1705 1710Arg Arg Arg Gly Arg Asn Leu Thr Val Thr Cys Asp Glu Arg Glu 1715 1720 1725Gly Asn Ile Thr Pro Met Ala Ser Val Arg Phe Phe Arg Ala Glu 1730 1735 1740Leu Cys Pro Val Val Gln Glu Thr Ala Glu Thr Arg Asp Thr Ala 1745 1750 1755Met Ser Leu Gln Ala Pro Pro Ser Thr Ala Thr Glu Pro Asn His 1760 1765 1770Pro Pro Ile Ser Phe Gly Ala Ser Ser Glu Thr Phe Pro Ile Thr 1775 1780 1785Phe Gly Asp Phe Asn Glu Gly Glu Ile Glu Ser Leu Ser Ser Glu 1790 1795 1800Leu Leu Thr Phe Gly Asp Phe Leu Pro Gly Glu Val Asp Asp Leu 1805 1810 1815Thr Asp Ser Asp Trp Ser Thr Cys Ser Asp Thr Asp Asp Glu Leu 1820 1825 1830Leu Asp Arg Ala Gly Gly Tyr Ile Phe Ser Ser Asp Thr Gly Pro 1835 1840 1845Gly His Leu Gln Gln Lys Ser Val Arg Gln Ser Val Leu Pro Val 1850 1855 1860Asn Thr Leu Glu Glu Val His Glu Glu Lys Cys Tyr Pro Pro Lys 1865 1870 1875Leu Asp Glu Ala Lys Glu Gln Leu Leu Leu Lys Lys Leu Gln Glu 1880 1885 1890Ser Ala Ser Met Ala Asn Arg Ser Arg Tyr Gln Ser Arg Lys Val 1895 1900 1905Glu Asn Met Lys Ala Ala Ile Ile Gln Arg Leu Lys Arg Gly Cys 1910 1915 1920Arg Leu Tyr Leu Met Ser Glu Thr Pro Lys Val Pro Thr Tyr Arg 1925 1930 1935Thr Thr Tyr Pro Ala Pro Val Tyr Ser Pro Pro Ile Asn Val Arg 1940 1945 1950Leu Ser Asn Pro Glu Ser Ala Val Ala Ala Cys Asn Glu Phe Leu 1955 1960 1965Ala Arg Asn Tyr Pro Thr Val Ser Ser Tyr Gln Ile Thr Asp Glu 1970 1975 1980Tyr Asp Ala Tyr Leu Asp Met Val Asp Gly Ser Glu Ser Cys Leu 1985 1990 1995Asp Arg Ala Thr Phe Asn Pro Ser Lys Leu Arg Ser Tyr Pro Lys 2000 2005 2010Gln His Ala Tyr His Ala Pro Ser Ile Arg Ser Ala Val Pro Ser 2015 2020 2025Pro Phe Gln Asn Thr Leu Gln Asn Val Leu Ala Ala Ala Thr Lys 2030 2035 2040Arg Asn Cys Asn Val Thr Gln Met Arg Glu Leu Pro Thr Leu Asp 2045 2050 2055Ser Ala Val Phe Asn Val Glu Cys Phe Lys Lys Phe Ala Cys Asn 2060 2065 2070Gln Glu Tyr Trp Glu Glu Phe Ala Ala Ser Pro Ile Arg Ile Thr 2075 2080 2085Thr Glu Asn Leu Ala Thr Tyr Val Thr Lys Leu Lys Gly Pro Lys 2090 2095 2100Ala Ala Ala Leu Phe Ala Lys Thr His Asn Leu Leu Pro Leu Gln 2105 2110 2115Glu Val Pro Met Asp Arg Phe Thr Val Asp Met Lys Arg Asp Val 2120 2125 2130Lys Val Thr Pro Gly Thr Lys His Thr Glu Glu Arg Pro Lys Val 2135 2140 2145Gln Val Ile Gln Ala Ala Glu Pro Leu Ala Thr Ala Tyr Leu Cys 2150 2155 2160Gly Ile His Arg Glu Leu Val Arg Arg Leu Asn Ala Val Leu Leu 2165 2170 2175Pro Asn Val His Thr Leu Phe Asp Met Ser Ala Glu Asp Phe Asp 2180 2185 2190Ala Ile Ile Ala Ala His Phe Lys Pro Gly Asp Thr Val Leu Glu 2195 2200 2205Thr Asp Ile Ala Ser Phe Asp Lys Ser Gln Asp Asp Ser Leu Ala 2210 2215 2220Leu Thr Ala Leu Met Leu Leu Glu Asp Leu Gly Val Asp His Ser 2225 2230 2235Leu Leu Asp Leu Ile Glu Ala Ala Phe Gly Glu Ile Ser Ser Cys 2240 2245 2250His Leu Pro Thr Gly Thr Arg Phe Lys Phe Gly Ala Met Met Lys 2255 2260 2265Ser Gly Met Phe Leu Thr Leu Phe Val Asn Thr Leu Leu Asn Ile 2270 2275 2280Thr Ile Ala Ser Arg Val Leu Glu Asp Arg Leu Thr Lys Ser Ala 2285 2290 2295Cys Ala Ala Phe Ile Gly Asp Asp Asn Ile Ile His Gly Val Val 2300 2305 2310Ser Asp Glu Leu Met Ala Ala Arg Cys Ala Thr Trp Met Asn Met 2315 2320 2325Glu Val Lys Ile Ile Asp Ala Val Val Ser Leu Lys Ala Pro Tyr 2330 2335 2340Phe Cys Gly Gly Phe Ile Leu His Asp Thr Val Thr Gly Thr Ala 2345 2350 2355Cys Arg Val Ala Asp Pro Leu Lys Arg Leu Phe Lys Leu Gly Lys 2360 2365 2370Pro Leu Ala Ala Gly Asp Glu Gln Asp Glu Asp Arg Arg Arg Ala 2375 2380 2385Leu Ala Asp Glu Val Ile Arg Trp Gln Arg Thr Gly Leu Ile Asp 2390 2395 2400Glu Leu Glu Lys Ala Val Tyr Ser Arg Tyr Glu Val Gln Gly Ile 2405 2410 2415Ser Val Val Val Met Ser Met Ala Thr Phe Ala Ser Ser Arg Ser 2420 2425 2430Asn Phe Glu Lys Leu Arg Gly Pro Val Ile Thr Leu Tyr Gly Gly 2435 2440 2445Pro Lys 24507943DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 79aaaaaagatc tgacaacttc aatgtctata aagccacaag acc 438046DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 80tttttgcggc cgcgtcatag tagggtacag ctcataatag tacaag 468163DNAChikungunya virusCDS(13)..(63) 81cgcagcacca ag gac aac ttc aat gtc tat aaa gcc aca aga cca tac cta 51 Asp Asn Phe Asn

Val Tyr Lys Ala Thr Arg Pro Tyr Leu 1 5 10gct cac tgt cca 63Ala His Cys Pro 158263DNAChikungunya virusCDS(1)..(63) 82ccg cat gag ata atc ttg tac tat tat gag ctg tac cct act atg act 48Pro His Glu Ile Ile Leu Tyr Tyr Tyr Glu Leu Tyr Pro Thr Met Thr1 5 10 15gta gta gtt gtg tca 63Val Val Val Val Ser 208317PRTChikungunya virus 83Asp Asn Phe Asn Val Tyr Lys Ala Thr Arg Pro Tyr Leu Ala His Cys1 5 10 15Pro8421PRTChikungunya virus 84Pro His Glu Ile Ile Leu Tyr Tyr Tyr Glu Leu Tyr Pro Thr Met Thr1 5 10 15Val Val Val Val Ser 20851161DNAChikungunya virusCDS(13)..(1155) 85ggatccgcca cc atg ctg ctg agc gtg ccc ctg ctg ctg ggc ctg ctg ggc 51 Met Leu Leu Ser Val Pro Leu Leu Leu Gly Leu Leu Gly 1 5 10ctg gcc gtg gac aac ttc aac gtg tac aag gct acc aga ccc tac ctg 99Leu Ala Val Asp Asn Phe Asn Val Tyr Lys Ala Thr Arg Pro Tyr Leu 15 20 25gcc cac tgc ccc gac tgc ggc gag gga cac agc tgc cac agc ccc gtg 147Ala His Cys Pro Asp Cys Gly Glu Gly His Ser Cys His Ser Pro Val30 35 40 45gcc ctg gag aga atc cgg aac gag gct acc gac ggc acc ctg aag atc 195Ala Leu Glu Arg Ile Arg Asn Glu Ala Thr Asp Gly Thr Leu Lys Ile 50 55 60cag gtg agc ctg cag atc ggc atc aag acc gac gac agc cac gac tgg 243Gln Val Ser Leu Gln Ile Gly Ile Lys Thr Asp Asp Ser His Asp Trp 65 70 75acc aag ctg aga tac atg gac aac cac atg ccc gcc gac gcc gag aga 291Thr Lys Leu Arg Tyr Met Asp Asn His Met Pro Ala Asp Ala Glu Arg 80 85 90gcc ggc ctg ttc gtg aga acc agc gcc ccc tgc acc atc acc ggc acc 339Ala Gly Leu Phe Val Arg Thr Ser Ala Pro Cys Thr Ile Thr Gly Thr 95 100 105atg ggc cac ttc atc ctg gcc aga tgc ccc aag ggc gag acc ctg acc 387Met Gly His Phe Ile Leu Ala Arg Cys Pro Lys Gly Glu Thr Leu Thr110 115 120 125gtg ggc ttc acc gac agc aga aag atc agc cac agc tgc acc cac ccc 435Val Gly Phe Thr Asp Ser Arg Lys Ile Ser His Ser Cys Thr His Pro 130 135 140ttc cac cac gac cct ccc gtg atc ggc aga gag aag ttc cac agc aga 483Phe His His Asp Pro Pro Val Ile Gly Arg Glu Lys Phe His Ser Arg 145 150 155ccc cag cac ggc aag gag ctg ccc tgc agc acc tac gtg cag agc acc 531Pro Gln His Gly Lys Glu Leu Pro Cys Ser Thr Tyr Val Gln Ser Thr 160 165 170gcc gct aca acc gag gag atc gag gtg cac atg ccc ccc gac acc ccc 579Ala Ala Thr Thr Glu Glu Ile Glu Val His Met Pro Pro Asp Thr Pro 175 180 185gac aga acc ctg atg agc cag cag agc ggc aac gtg aag atc acc gtg 627Asp Arg Thr Leu Met Ser Gln Gln Ser Gly Asn Val Lys Ile Thr Val190 195 200 205aac ggc cag acc gtg aga tac aag tgc aac tgc ggc ggc agc aac gag 675Asn Gly Gln Thr Val Arg Tyr Lys Cys Asn Cys Gly Gly Ser Asn Glu 210 215 220ggc ctg acc aca acc gac aag gtg atc aac aac tgc aag gtg gac cag 723Gly Leu Thr Thr Thr Asp Lys Val Ile Asn Asn Cys Lys Val Asp Gln 225 230 235tgc cac gcc gcc gtg acc aac cac aag aag tgg cag tac aac agc ccc 771Cys His Ala Ala Val Thr Asn His Lys Lys Trp Gln Tyr Asn Ser Pro 240 245 250ctg gtg ccc aga aac gcc gag ctg ggc gac aga aag ggc aag atc cac 819Leu Val Pro Arg Asn Ala Glu Leu Gly Asp Arg Lys Gly Lys Ile His 255 260 265atc ccc ttc ccc ctg gcc aac gtg acc tgc aga gtg ccc aag gcc aga 867Ile Pro Phe Pro Leu Ala Asn Val Thr Cys Arg Val Pro Lys Ala Arg270 275 280 285aac ccc acc gtg acc tac ggc aag aac cag gtg atc atg ctg ctg tac 915Asn Pro Thr Val Thr Tyr Gly Lys Asn Gln Val Ile Met Leu Leu Tyr 290 295 300ccc gat cac ccc acc ctg ctg agc tac aga aac atg ggc gag gag ccc 963Pro Asp His Pro Thr Leu Leu Ser Tyr Arg Asn Met Gly Glu Glu Pro 305 310 315aac tac cag gag gag tgg gtg atg cac aag aag gag gtg gtg ctg acc 1011Asn Tyr Gln Glu Glu Trp Val Met His Lys Lys Glu Val Val Leu Thr 320 325 330gtg ccc acc gag ggc ctg gag gtg acc tgg ggc aac aac gag ccc tac 1059Val Pro Thr Glu Gly Leu Glu Val Thr Trp Gly Asn Asn Glu Pro Tyr 335 340 345aag tac tgg ccc cag ctg agc acc aac ggc acc gcc cac gga cac ccc 1107Lys Tyr Trp Pro Gln Leu Ser Thr Asn Gly Thr Ala His Gly His Pro350 355 360 365cac gag atc atc ctg tac tac tac gag ctg tac ccc acc atg acc tga 1155His Glu Ile Ile Leu Tyr Tyr Tyr Glu Leu Tyr Pro Thr Met Thr 370 375 380ctcgag 116186380PRTChikungunya virus 86Met Leu Leu Ser Val Pro Leu Leu Leu Gly Leu Leu Gly Leu Ala Val1 5 10 15Asp Asn Phe Asn Val Tyr Lys Ala Thr Arg Pro Tyr Leu Ala His Cys 20 25 30Pro Asp Cys Gly Glu Gly His Ser Cys His Ser Pro Val Ala Leu Glu 35 40 45Arg Ile Arg Asn Glu Ala Thr Asp Gly Thr Leu Lys Ile Gln Val Ser 50 55 60Leu Gln Ile Gly Ile Lys Thr Asp Asp Ser His Asp Trp Thr Lys Leu65 70 75 80Arg Tyr Met Asp Asn His Met Pro Ala Asp Ala Glu Arg Ala Gly Leu 85 90 95Phe Val Arg Thr Ser Ala Pro Cys Thr Ile Thr Gly Thr Met Gly His 100 105 110Phe Ile Leu Ala Arg Cys Pro Lys Gly Glu Thr Leu Thr Val Gly Phe 115 120 125Thr Asp Ser Arg Lys Ile Ser His Ser Cys Thr His Pro Phe His His 130 135 140Asp Pro Pro Val Ile Gly Arg Glu Lys Phe His Ser Arg Pro Gln His145 150 155 160Gly Lys Glu Leu Pro Cys Ser Thr Tyr Val Gln Ser Thr Ala Ala Thr 165 170 175Thr Glu Glu Ile Glu Val His Met Pro Pro Asp Thr Pro Asp Arg Thr 180 185 190Leu Met Ser Gln Gln Ser Gly Asn Val Lys Ile Thr Val Asn Gly Gln 195 200 205Thr Val Arg Tyr Lys Cys Asn Cys Gly Gly Ser Asn Glu Gly Leu Thr 210 215 220Thr Thr Asp Lys Val Ile Asn Asn Cys Lys Val Asp Gln Cys His Ala225 230 235 240Ala Val Thr Asn His Lys Lys Trp Gln Tyr Asn Ser Pro Leu Val Pro 245 250 255Arg Asn Ala Glu Leu Gly Asp Arg Lys Gly Lys Ile His Ile Pro Phe 260 265 270Pro Leu Ala Asn Val Thr Cys Arg Val Pro Lys Ala Arg Asn Pro Thr 275 280 285Val Thr Tyr Gly Lys Asn Gln Val Ile Met Leu Leu Tyr Pro Asp His 290 295 300Pro Thr Leu Leu Ser Tyr Arg Asn Met Gly Glu Glu Pro Asn Tyr Gln305 310 315 320Glu Glu Trp Val Met His Lys Lys Glu Val Val Leu Thr Val Pro Thr 325 330 335Glu Gly Leu Glu Val Thr Trp Gly Asn Asn Glu Pro Tyr Lys Tyr Trp 340 345 350Pro Gln Leu Ser Thr Asn Gly Thr Ala His Gly His Pro His Glu Ile 355 360 365Ile Leu Tyr Tyr Tyr Glu Leu Tyr Pro Thr Met Thr 370 375 3808759DNAChikungunya virus 87tatagatcaa agggctacgc aacccctgaa tagtaacaaa atacaaaatc actaaaaat 598860DNAChikungunya virus 88tatagatcaa agggccgaat aacccctgaa tagtaacaaa atatgaaaat caataaaaat 608959DNAChikungunya virus 89agtagttcaa agggctataa aacccctgaa tagtaacaaa acataaaatt aataaaaat 599059DNAChikungunya virus 90tctagatcaa agggctatat aacccctgaa tagtaacaaa atacaaaatc actaaaaat 599160DNAChikungunya virus 91tatagatcaa agggccgaac aacccctgaa tagtaacaaa atataaaaat taataaaaat 609260DNAChikungunya virus 92agtagttcaa agggctataa aaacccctga atagtaacaa aacataaaac taataaaaat 609360DNAChikungunya virus 93attagatcaa agggctatac aacccctgaa tagtaacaaa acacaaaaac caataaaaat 609460DNAChikungunya virus 94tatagatcaa agggctatat taacccctga atagtaacaa aacacaaaaa caataaaaac 609560DNAChikungunya virus 95agtagttcaa agggctacaa aacccctgaa tagtaacaaa acataaaatg taataaaaat 609660DNAChikungunya virus 96agtagttcaa agggctataa aaacccctga atagtaacaa aacataaaac taataaaaat 609760DNAChikungunya virus 97tatagatcaa aggcttgaat aacccctgaa taataataaa atataaaaat aaataagaat 609859DNAChikungunya virus 98agatgttcaa agtggctata aaaccctgaa tagtaataaa acataaaatt aataaggat 599959DNAChikungunya virus 99tgtagatcaa agggctatat aacccctgaa tagtaacaaa atacaaaatc actaaaaat 5910061DNAChikungunya virus 100agtagttcaa agggctataa aaacccctga atagtaacaa aacataaaac ctaataaaga 60t 6110160DNAChikungunya virus 101agatgttcaa agtggctata aaacccctga atagtaataa aacataaaat taataaggat 6010226RNAArtificial SequenceDescription of Artificial Sequence Synthetic oligonucleotide 102uaagucccca acgcaucggg aaacua 2610360DNAChikungunya virus 103ccgcatgaga taatcttgta ctattatgag ctgtacccta ctatgacgcg gccgcaaaaa 60

Claims

1. An isolated and purified wild strain of chikungunya virus (CHIKV) capable of in vitro infecting human cells.

2. The strain according to claim 1, selected from the group consisting of the isolates 05.115, 05.61, 05.209, 06.21, 06.27 and 06.49.

3. The strain according to claim 1 or 2, wherein its genome comprises a sequence as shown in FIG. 4 (SEQ ID NO:1).

4. The strain according to claim 1 or 2, wherein its genome comprises a sequence as shown in FIG. 5 (SEQ ID NO:2).

5. The strain according to claim 1 or 2, wherein its genome comprises a sequence as shown in FIG. 6 (SEQ ID NO:3).

6. The strain according to claim 1 or 2, wherein its genome comprises a sequence as shown in FIG. 7 (SEQ ID NO:4).

7. The strain according to claim 1 or 2, wherein its genome comprises a sequence as shown in FIG. 8 (SEQ ID NO:5).

8. The strain according to claim 1 or 2, wherein its genome comprises a sequence as shown in FIG. 9 (SEQ ID NO:6).

9. An isolated and purified strain of chikungunya virus (CHIKV) comprising at least one mutation in structural protein E1 and/or structural protein E2.

10. The strain of claim 9, wherein the at least one mutation is located in the ectodomain of protein E 1 and/or E2.

11. The strain of claim 9 or 10, wherein the at least one mutation in the E2 protein is a mutation at a position homologous to amino acid position 382, 399, 404, 485, 489, 506, 536, 624, 637, 669, 700 or 711 of SEQ ID NO: 23.

12. The strain of claim 11, wherein the mutation is G382K.

13. The strain of claim 11, wherein the mutation is 1399M.

14. The strain of claim 11, wherein the mutation is G404E.

15. The strain of claim 11, wherein the mutation is N495T.

16. The strain of claim 11, wherein the mutation is A489T.

17. The strain of claim 11, wherein the mutation is L506M.

18. The strain of claim 11, wherein the mutation is 1536T.

19. The strain of claim 11, wherein the mutation is S624N.

20. The strain of claim 11, wherein the mutation is T637M.

21. The strain of claim 11, wherein the mutation is A669T.

22. The strain of claim 11, wherein the mutation is S700T.

23. The strain of claim 11, wherein the mutation is V711A.

24. The strain of claim 9 or 10, wherein the at least one mutation in the E1 protein is a mutation at a position homologous to amino acid position 1035, 1078, 1093 or 1131 of SEQ ID NO: 23.

25. The strain of claim 24, wherein the mutation is A1035V.

26. The strain of claim 24, wherein the mutation is M1078V.

27. The strain of claim 24, wherein the mutation is D1093E.

28. The strain of claim 24, wherein mutation is V1131A.

29. An isolated and purified polynucleotide comprising all or part of the sequence as shown in FIG. 4, 5, 6, 7, 8 or 9 (SEQ ID NOS 1, 2, 3, 4, 5 or 6).

30. Fragment of the polynucleotide as defined in claim 29, wherein it codes for the ectodomain of glycoprotein E2.

31. The fragment of claim 30, wherein it comprises a nucleotide sequence as shown in FIG. 10, 11, 12 or 13 (SEQ 10 NOS 7, 8, 9 or 10).

32. Fragment of the polynucleotide as defined in claim 29, wherein it codes for a soluble form of glycoprotein E2.

33. The fragment of claim 32, wherein it consists of a nucleotide sequence as shown in FIG. 14, 15, 16 or 17 (SEQ ID NOS 11, 12, 13 or 14).

34. The fragment of the polynucleotide as defined in claim 29, wherein it codes for the ectodomain of glycoprotein E1.

35. A vector comprising a fragment as defined in any one of claims 30 to 34.

36. A plasmid comprising a fragment as defined in claim 31, selected from the group deposited at the CNCM (Collection Nationale de Cultures de Microorganismes), 28 rue du Docteur Roux, 75724 PARIS Cedex 15, France, on Mar. 15, 2006 under accession number 1-3587, 1-3588, 1-3589 and 1-3590.

37. A plasmid comprising a fragment as defined in claim 33, wherein the sequence in optimised for efficient production of recombinant E2 protein deposited at the CNCM (Collection Nationale de Cultures de Microorganismes), 28 rue du Oocteur Raux, 75724 PARIS Cedex 15, France, on Mar. 14, 2007, under accession number 1-3733.

38. A host cell comprising a vector as defined in claim 35.

39. A host cell comprising a plasmid as defined in claim 36 or 37.

40. A purified polypeptide encoded by a polynucleotide as defined in claim 29, or by a fragment as defined in anyone of claims 30 to 34.

41. A purified polypeptide comprising all or part of the sequence as defined in FIGS. 38 to 49 (SEQ ID NOS: 24 to 34 and 78)

42. A purified polypeptide comprising all or part of the sequence as defined in FIG. 18, 19, 20 or 21 (SEQ ID NOS 15, 16, 17, or 18).

43. A purified polypeptide comprising all or part of the sequence as defined in FIG. 22, 23, 24 or 25 (SEQ ID NOS 19, 20, 21, or 22).

44. Monoclonal or polyclonal antibodies, or fragment thereof, that specifically bind to a polypeptide as defined in anyone of claims 40 to 43.

45. (canceled)

46. (canceled)

47. A composition comprising at least one element selected from the group consisting of:a strain as defined in anyone of claims 1 to 28;a polynucleotide as defined in claim 29;a fragment as defined in anyone of claims 30 to 34;a vector as defined in anyone of claims 35 to 37;a plasmid as defined in claim 36 or 37;a host cell as defined in claim 38 or 39;a polypeptide as defined in anyone of claims 40 to 43; andan antibody as defined in claim 44;for treating and/or preventing an arbovirosis.

48. (canceled)

49. A kit for the detection of a CHIKV associated to an arbovirosis, comprising at least one element selected from the group consisting of:a strain as defined in anyone of claims 1 to 28;a polynucleotide as defined in claim 29;a fragment as defined in anyone of claims 30 to 34;a vector as defined in anyone of claims 35 to 37;a plasmid as defined in claim 36 or 37;a host cell as defined in claim 38 or 39;a polypeptide as defined in anyone of claims 40 to 43; andan antibody as defined in claim 44.

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