Patent application title: RECOMBINANT VECTOR CONTAINING INFECTIOUS HUMAN CYTOMEGALOVIRUS GENOME WITH PRESERVED WILD-TYPE CHARACTERISTICS OF CLINICAL ISOLATES
Inventors:
Gabriele Hahn (Munchen, DE)
Assignees:
Vical Incorporated
Wistar Institute
IPC8 Class: AC12N121FI
USPC Class:
43525233
Class name: Bacteria or actinomycetales; media therefor transformants (e.g., recombinant dna or vector or foreign or exogenous gene containing, fused bacteria, etc.) escherichia (e.g., e. coli, etc.)
Publication date: 2010-10-21
Patent application number: 20100267121
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Patent application title: RECOMBINANT VECTOR CONTAINING INFECTIOUS HUMAN CYTOMEGALOVIRUS GENOME WITH PRESERVED WILD-TYPE CHARACTERISTICS OF CLINICAL ISOLATES
Inventors:
Gabriele Hahn
Agents:
SUGHRUE MION, PLLC
Assignees:
Origin: WASHINGTON, DC US
IPC8 Class: AC12N121FI
USPC Class:
Publication date: 10/21/2010
Patent application number: 20100267121
Abstract:
A recombinant vector containing infectious genome of human cytomegalovirus
(HCMV) and being useful for the production of reconstituted HCMV virus
retaining phenotypic characteristics of a clinical virus isolate
including the ability to grow on endothelial cells and to induce
microfusion is characterized in that it is obtainable by inserting DNA
from a clinical isolate of HCMV virus into a bacterial cloning vehicle.
Such vector can be used e.g., for production of reconstituted HCMV virus
retaining the phenotypic characteristics of a parental clinical isolate
and for studying genes and functions of genes of HCMV virus. A further
aspect are mutant viruses and inter alia their use for studying aspects
of infectivity of HCMV virus.Claims:
1. Recombinant vector containing infectious genome of human
cytomegalovirus (HCMV) and being useful for the production of
reconstituted HCMV virus retaining phenotypic characteristics of a
clinical virus isolate including the ability to grow on endothelial
cells, to induce microfusion and to spread viral material from HUVEC to
PMNL, characterized in that it is obtainable by inserting DNA from a
clinical isolate of HCMV virus into a bacterial cloning vehicle.
2. Recombinant vector according to claim 1 which contains the complete infectious DNA of HCMV.
3. Recombinant vector according to claim 1, characterized in that the bacterial cloning vehicle contains DNA sequences which are homologous to the HCMV DNA and insertion is effected by homologous recombination.
4. Recombinant vector according to claim 1, wherein the bacterial cloning vehicle is a BAC system vector.
5. Recombinant vector according to claim 1 and designated FIX-Bac-7.
6. Bacterial cell line containing a recombinant vector according to claim 1.
7. Bacterial cell line according to claim 6 which is an E. coli cell line.
8. Bacterial cell line according to claim 6, designated FIX-Bac-7-E. coli DH 10B and deposited as DSM 13958 containing at least one copy of FIX-Bac-7.
9. A bacterial cell line according to claim 6 for the production of reconstituted HCMV Virus retaining the phenotypic characteristics of a parental clinical isolate including the ability to grow on endothelial cells, to induce microfusion and to spread viral material from HUVEC to PMNL.
Description:
[0001]This is a continuation of application Ser. No. 11/180,000 filed Jul.
13, 2005 (which issued on Mar. 31, 2010 as U.S. Pat. No. 7,700,350),
which is a continuation of application Ser. No. 10/275,287 filed November
2002 (now abandoned), which is a 371 of PCT/EP02/01867 filed Feb. 21,
2002. The disclosure of the prior applications is hereby incorporated by
reference in its entirety.
[0002]The present invention is concerned with recombinant vectors containing infectious genome sequences of human cytomegalovirus (HCMV) and being useful for the production of reconstituted HCMV virus retaining phenotypic characteristics of a clinical virus isolate including the ability to grow on endothelial cells and to induce microfusion events. Further, the invention concerns the use of such recombinant vectors for the production of reconstituted HCMV virus with the mentioned characteristics as well as the use of reconstituted infectious HCMV virus for the production of vaccines and/or antibodies against the virus. Further embodiments of the invention are the use of reconstituted virus for the screening of drugs, the use of the recombinant vector and/or the reconstituted virus for studying genes and function of genes, as well as other uses. A further subject of the present invention are HCMV virus mutants, in which the region UL130 to UL132 is either deleted or mutated in such a way that the ability to induce microfusion events is lost or in which the region UL128 to UL132 is deleted or mutated in such a way that PMNL (polymorphonuclear leukocytes) and/or HUVEC (human umbilical vein endothelial cells) tropism is reduced or lost. Further embodiments are uses of such virus mutants or transfer of the genetic region UL132-128 of FIX-Bac into fibroblast adapted laboratory strains of HCMV (for example AD169) to regain PMNL and HUVEC tropism.
[0003]HCMV is a leading cause of birth defects when infection is acquired by HCMV-seronegative women during pregnancy (refs 1,2,3). In addition, HCMV represents one of the major opportunistic pathogens in immunocompromised individuals, such as bone marrow and solid organs transplant recipients and patients with primary or acquired (AIDS) immune deficiency. However, the pathogenesis of HCMV infection is not well understood. The main factor affecting research on this topic is recognized in the lack of the possibility of reproducing in vitro aspects of HCMV infection which are thought to be crucial in vivo. In particular, HCMV has been demonstrated to be able to infect in vivo several tissues and a number of cell types (refs 1,4), providing a wide spectrum of symptomatic diseases and organ localizations in immunocompromised individuals (refs 5,6) or inducing defects in multiple organs during embryogenesis which can be summarized as "congenital HCMV syndrome". In addition, a striking in vivo characteristic of primary HCMV infection in immunocompetent individuals (ref 7) and of active HCMV infection in immunocompromised patients (ref 8), is the presence of infectious virus and viral materials in circulating polymorphonuclear leukocytes (PMNL) (refs 9,10). The latter is a major prognostic marker, which is highly predictive of disease progression in immunocompromised patients. Provided that the virus does not appear to fully replicate in PMNL, rather it can actively promote transfer of preformed viral particles to PMNL from productively infected cells by virus-induced microfusion events (ref 11), HCMV-positive PMNL are a powerful vehicle for viral dissemination.
[0004]In contrast, currently available HCMV laboratory-adapted reference strains (AD 169, Towne, Davis and Toledo) (refs 12, 13) lost phenotypic characteristics thought to be important for pathogenicity"in vivo". Examples of pathogenic characteristics of clinical isolates are: i) preferential cell-to-cell spread, ii) tropism for a broad spectrum of tissues, iii) ability to transfer infectious virus to PMNL. Laboratory-adapted strains lost these biologic characteristics during propagation in standard cell culture (human embryonic fibroblasts, HEF). In addition, reference strains show a different genome organization with respect to clinical strains. In fact, clinical strains have 13.5 kb of additional genome sequence which present a particular orientation in clinical strains. Moreover, due to the intrinsic slow HCMV replication in cell culture, the generation of mutants for studying different phenotypic characteristics is extremely cumbersome and time consuming.
[0005]Consequently, it was the object of the present invention to provide a possibility to in vitro produce HCMV virus that still retains the pathogenic characteristics of clinical isolates. Further objects of the invention are to provide vectors containing the viral genome that allow to mutagenize the viral genome for e.g. studying the function of specific regions of the genome or to provide for mutated virus that can be used e.g. for vaccine production.
[0006]These objects are solved by the present invention as described in the following: A first subject of the present invention is a recombinant vector containing DNA sequences of human cytomegalovirus (HCMV) and being useful for the production of reconstituted HCMV virus retaining phenotypic characteristics of a clinical virus isolate including the ability to grow on endothelial cells and to induce microfusion events, such recombinant vector being characterized in that it is obtainable by inserting the infectious genome from a clinical isolate of HCMV virus into a bacterial cloning vehicle.
[0007]Within the context of the present invention it has been observed that low passage clinical isolates retained both the broad cell tropism observed in vivo and the capability to transfer virus via microfusion to PMNL (ref 11). The invention is based on the surprising finding that cloning clinical isolates of HCMV virus in the so-called BAC system (WO99/06582) provides for the first time the possibility to in vitro produce HCMV virus that shows at least the most important characteristics of HCMV virus. These are above all the ability to grow on endothelial cells and to induce microfusion events to promote transfer of viral particles between cells. From the standpoint of the present knowledge about HCMV infection, these two characteristics seem to be most important for the infectivity of wild-type virus. Especially the use of the BAC system opens the possibility of propagation of stable HCMV genetic material in a heterologous biological system as e.g. E. coli. In particular, the accumulation of mutations during the HEF adaption procedure, which is ultimately responsible for the loss of broad tissue tropism by presently available reference laboratory adapted strains, is avoided. Thus, a recombinant vector according to the present invention provides the possibility to in vitro produce a new reference strain for genetic analysis of HCMV strains circulating in vivo. The vector according to the present invention provides a genetic background encoding phenotypic characteristics crucial for HCMV pathogenesis in vivo.
[0008]The recombinant vector according to the invention, apart from providing the possibility to produce infectious virus in vitro, also represents a unique reagent for identifying viral genes and viral gene functions, which are crucial for HCMV pathogenesis. In fact, it retains the complete gene structure of HCMV strains present in vivo and virus produced therefrom retains key known pathogenetic characteristics, namely endothelial cell tropism and microfusion phenotype and most likely others like Nk-cell resistance and infection of broncho-epithelial cells and chondrocytes as well as dendritic cells, monocytes and/or macrophages. Maintainance and replication of the recombinant vector including the viral genome is dissociated from replication of the virus in cell culture, but is preserved by replication of the viral DNA in the bacterial system. This provides a solution to obtaining standard genetic material for biological studies.
[0009]In a preferred embodiment of the present invention the recombinant vector contains the complete infectious genome of HCMV and lacks only genes US2-US6 which are not required for virus replication nor for HUVEC or PMNL tropism. However, it is also possible to produce mutants that lack at least part of the DNA or contain substitutions in the DNA. In this way, virus mutants can be produced specifically by deleting or substituting parts of the DNA. This allows to study and map the gene functions of HCMV easily. In principle any bacterial cloning system can be used to insert HCMV DNA, as long as it retains the ability for DNA replication in suitable host cells and is able to coreplicate the viral DNA. It is preferred to use cloning vehicles that are present with a low copy number in the host cell to achieve better stability of the viral sequences in the recombinant vector.
[0010]In a further preferred embodiment the recombinant vector according to the invention is produced using a bacterial cloning vehicle that contains DNA sequences which are homologous to the HCMV DNA and insertion is effected by homologous recombination. In an especially preferred embodiment the bacterial cloning vehicle is a BAC system vector, as described in WO99/06582, which is already mentioned above. The disclosure of WO99/06582, especially as far as it relates to the preparation of vectors and insertion of viral genome, is herewith incorporated by reference.
[0011]An especially preferred recombinant vector is designated FIX-Bac-7 and has been deposited as described in the following. This recombinant vector is especially useful for studying functions of HCMV virus or producing HCMV virus, since it contains an infectious HCMV virus genome with preserved wildtyp characteristics stably integrated into a BAC system vector. FIX-Bac-7-vector can be propagated like a normal recombinant vector and does not lose the viral DNA or functions.
[0012]A further subject of the present invention is a bacterial culture which contains a recombinant vector according to the invention. Such bacterial culture is able to reproduce recombinant vector and preferably such a bacterial culture is an E. coli cell line, especially E. coli DH10B. In a most preferred embodiment such bacterial culture according to the invention contains at least one copy of FIX-Bac-7, and is designated FIX-Bac-7-E. coli DH10B. This cell line has been deposited with the Deutsche Sammlung von Mikroorganismen and Zellkulturen GmbH-DSZM as DSM 13958 on Dec. 14, 2000.
[0013]Further subjects of the present invention are uses of the recombinant vector according to the invention. One preferred use is the production of reconstituted HCMV virus retaining the phenotypic characteristics of a parental clinical isolate including the ability to grow on endothelial cells and to induce microfusion.
[0014]As described above, these two characteristics are considered as being most important for retaining the infectivity of wild-type HCMV. However, it is to be understood that within the context of the present invention also other characteristics of wild-type virus may be conserved during the production as described in claim. Especially features like HUVEC- and/or PMNL-tropism are also considered important and are preferably retained by the HCMV virus which is reconstituted according to the present invention.
[0015]For the production of reconstituted HCMV virus it is preferred to transfect the recombinant vector into a suitable eukaryotic host cell and collect the reconstituted infectious virus after culturing of the cells.
[0016]A suitable eukaryotic host cell is a permissive cell which allows the virus to replicate and virus particles being formed. The reconstituted infectious HCMV virus obtained according to the present invention can e.g. be used for the production of vaccines and/or antibodies. It can also be used for the screening of drugs for their antiviral activity as well as generally for other potential uses of virus. Such uses are further subjects of the present invention. It has been observed that in some cases the packaging of the virus particles is impaired, obviously due to the presence of vector sequences in addition to virus genome. In such a case it is preferred to remove the sequences of the cloning vehicle from the recombinant vector prior to replication and packaging. In such embodiment it is further preferred to use a cloning vehicle that contains flanking sequences which are homologous to sequences of the virus to allow the removal of at least part of the cloning vehicle by homologous recombination or to flank the Bac vector with IoxP sites for removal with cre recombinase. For virus production from the recombinant vector it is again referred to WO99/06582 describing such methods in principle.
[0017]Still further subjects of the present invention are the use of recombinant vectors according to the present invention for vaccine development and/or for the development and/or screening of substances which inhibit viral gene production on transcriptional and/or translational level.
[0018]The concept of prophylactic vaccination using live attenuated viral strains led in the early 70ies to the generation of the Towne strain, after extensive passaging (>135 passages) of a clinical isolate of fibroblast culture. This live vaccine, when administered to humans, proved to be ineffective at protecting individuals from HCMV infections (refs 14-20). Strikingly, infection with vaccinal strain could raise antibody titers as well as cellular response. However, these responses were not protective. Today it is known that the Towne strain lost large genomic regions during fibroblast adaption. Other approaches include subunit vaccines again targeting gene products identified and characterized in attenuated strains Finally, the generation of chimeric viruses using the Towne strain and a low passage isolate (Toledo) has been proposed (refs 12, 13), however, both Towne and Toledo lack key characteristics associated with HCMV pathogenesis in vivo. In particular, they lack both endothelial cell tropism and the microfusion phenotype. Thus, using such a vaccine it was not possible to raise an efficient immunologic response against these important viral encoded functions.
[0019]The identification of genetic determinants for tissue tropism and body dissemination will lead to the design of better prophylactic and therapeutic vaccines. In this respect, the identification of the genetic determinants for endothelial cell tropism and for transfer of virus from productively infected cells to PMNL appear of particular importance. In fact, it is known that during active HCMV infection in immunocompromised patients endothelial cells are productively infected, while it is thought that endothelium might be the major reservoir for latent HCMV infection (refs 1, 21-28). Finally, the importance of HCMV infected PMNL in viral dissemination is highlighted by (i) the possibility to detect such cells in immunocompetent persons only during primary infection, (ii) relation to viral transmission of HCMV to the fetus in pregnant women (refs 2,3,7,29) and (iii) the tight correlation between the number of HCMV infected PMNL and the severity of clinical symptoms (ref 30). It is therefore evident that production of vaccines by using either the recombinant vector according to the invention or reconstituted infectious HCMV virus that is produced according to the invention opens the possibility to raise vaccines that not only raise antibodies but also protect the patient against HCMV infections and its consequences.
[0020]For drug discovery as well as for vaccine production, determinants for viral pathogenicity will be obvious targets for chemotherapeutic intervention. The generation of target specific antiviral drugs can be achieved in different ways:
1. The identification of gene products responsible for crucial biological functions (tropism for particular cell types, microfusion) might lead to the reconstruction of biochemical systems for screening of large collections of compounds; helpful will also be a random transposon mutagenesis of FIX-Bac-7 and reconstitution of mutants from transposon libraries.2. Peptides or small molecules interfering with protein-protein interactions can be synthesized by available computer-assisted chemical modelling;3. Inhibition of viral gene product synthesis can be achieved by interference at transcriptional or translational level using established gene therapy approaches.
[0021]Therefore also the use of a recombinant vector or a reconstituted HCMV virus for the development and/or screening of substances which inhibit viral gene production on transcriptional and/or translational level are preferred embodiments of the present invention.
[0022]Within the investigational work of the present invention it has further been established that the region UL130 to UL132 of HCMV virus is responsible for the ability of the virus to induce microfusion events in PMNL and HUVEC tropism. Hence, a virus mutant which is deleted or mutated in this region of the viral genome in such a way that the ability to induce microfusion or HUVEC tropism is lost, is a further subject of the present invention. Such virus can easily be produced using the recombinant vector according to the present invention and deleting or mutating the mentioned region by methods that are known to the man in the art (see also Example 5). It is especially preferred to completely delete this region, however, partially deleting or mutating the region is also possible as long as the resulting mutant does not show microfusion induction or HUVEC tropism. Using the recombinant vector according to the present invention, it will be easily possible for the man in the art to track down the minimal mutation or deletion that is necessary to prevent induction of microfusion events or HUVEC tropism of a respective HCMV mutant.
[0023]It has further been established that the region UL128 to UL132 of HCMV virus is responsible for PMNL and/or HUVEC tropism. The genetic region spanning UL131 to UL128 seems to confer PMNL tropism, whereas HUVEC tropism is encoded within the genetic region of UL132 to UL128 genes. Mutants that contain deletions or mutations within this UL128 to UL132 region of HCMV virus are therefore another preferred embodiment of the present invention. Also for these mutants it is either possible to delete the complete region or to just partially delete or mutate the region and thereby reduce or prevent PMNL and/or HUVEC tropism.
[0024]Such HCMV virus mutants in comparison with RV-FIX-7 can advantageously be used for studying pathogenicity and its genetic basis. Especially studying interaction of adherent cells with wild-type virus in comparison with mutant virus will reveal further mechanisms of infection by HCMV virus. Such use of the mutants and RV-FIX-7 therefore are a further preferred embodiment of the present invention. The HCMV virus mutants which affect the genetic region UL132-128 of the invention, lacking the ability to induce microfusion, also have lost the ability to grow on endothelial cells. The cell tropism of this mutant is also changed. The virus mutant seems to indicate a potentially novel mechanism of HCMV infection by a cell to cell infection pathway not through the natural receptor but through cell fusion events. Thus, avoiding the need to exit the cell for reinfection, but rather spreading genetic material from cell to cell through a plasma bridge. Also these mutants and RV-FIX-7 are targets for the development of vaccines and/or antibodies or the design of small molecules and peptides. Such vaccines and antibodies will provide at least some protection against HCMV virus infection.
[0025]Further possible uses of the HCMV virus mutants and RV-FIX-7 according to the invention are use in diagnostics, for drug screening, as attenuation marker, for the development of modified vectors, for the development of peptides or antisense genes or antisense RNA, which block the activity of the microfusion gene and wild-type virus and/or for the screening for such peptides, antisense genes or antisense RNA. A still further use is the studying of innate as well as adapted immune surveillance and immune counterstrategies as e.g. NK-cell resistance of virally infected target cells, cytotoxic and helper T-cell recognition, impact of tissue tropism on HCMV latency and reactivation. Also studying the impact on classic (HLA-A,B,C) and non classic (HLA-E, HLA-G, MIC A/B) MHC regulation on infected target cells (fibroblasts, endothelial cells, dendritic cells, trophoblasts, bronchoepithelial cells, smooth muscle cells) as well as induction or prevention of apoptosis and cell suicide.
[0026]Such applications and uses will be well aware to the man in the art upon reading the disclosure of the present invention. Providing a stable system for in vitro production of infectious HCMV virus, tracking down the microfusion gene in the viral region UL131 to UL128 and the HUVEC cell tropism region between UL128 and UL132 as well as the provision of the possibility to easily produce virus mutants allow for the first time to study infectious HCMV virus activities and properties with a standardized virus strain, and the thus provided possibility to mutate in vitro a virus that corresponds to a clinical isolate opens tremendous possiblities for studying functions and ways of infections and their consequences for the infected person.
[0027]The possibility to produce infectious virus as well as mutants of infectious virus or antigens contained in the genome of the infectious virus opens new outlooks for vaccine development and drug design as well as drug screening
[0028]The examples of the present invention contain disclosure on several different mutants and transcriptional analyses that were used to track down the genetic regions responsible for microfusion as well as cell tropism. These mutants are especially preferred mutants according to the present invention and are further subjects of the present invention.
[0029]The present invention will be further explained by the following example and figures:
[0030]FIG. 1A-E:
[0031]HUVECs were infected with low MOI (1 A-B) or high MOI (1 C-D) with either clinical wild-type isolate VR1814 (1A-C) or bac-cloned and reconstituted virus RV-FIX-7 (1B-D). Staining was done with an ie1/2 mab as primary antibody and an anti-mouse peroxidase labelled mab as secondary antibody (1A-D). VR1814 (1E) or RV-FIX-7 (1 F) infected HUVECs were cocultivated with peripheral blood polymorphonuclear leukocytes (PMNL) and the lower matrix phosphoprotein (pp 65) was detected in the nuclei of PMNL by indirect immunofluorescence. FIGS. 1E-F demonstrate that RV-FIX-7 (1 F) retained the capability to infect HUVECs and induce microfusion as compared to WT virus VR1814 (1E).
[0032]The pp 65 staining was performed as described in Journal of Microbiology 36, 3585-3589, 1998.
[0033]FIG. 2
[0034]DNA derived from individually grown FIX-Bac clones (lanes 1-5 and lanes 7-11) or wild-type VR1814 (lanes 6 and 12) was digested with either EcoRI (lanes 1-6 or BgIII (lanes 7-12) and separated on a 0.5% agarose gel. The restriction cut and subsequent Southern Blot analyses confirmed the correct integration of the gpt-bac cassette between US1 and US7. In the EcoRI restriction cut a 5.9 kb band arises due to the integration of the gpt-Bac cassette. An "a" sequence polymorphism could also be confirmed which arises due to a shuffling of "a" sequences at the internal and terminal repeats during the replication of HCMV.
[0035]M: molecular weight marker 1 kb ladder.
[0036]Analyses were performed as previously described (Journal of Virology, 8320-8329, 1999).
[0037]FIG. 3
[0038]DNA derived from individually grown FIX-Bac-7 clones (lane 1 and 6) or FIX-Bac-7 mutant clones Δ-ULB' (lanes 2-3 and lanes 7-8) or ΔULB130-132 (lanes 4-5 and lanes 9-10) was digested with either HindIII (lanes 1-5) or BgIII (6-10), respectively, and run on a 0.5% agarose gel. A novel band at around 6.5 kb arises in both mutant clones in the HindIII restriction cut. An additional band at around 4.7 kb arises in the Δ-ULB' clones in the HindIII cut as compared to the parallel clone FIX-Bac-7. The generation and testing of the mutants is described in the text. M: molecular weight marker 1 kb ladder.
[0039]FIG. 4:
[0040]DNA derived from individually grown Towne-long-Bac (TowneL), Towne-short-Bac (TowneS), Phoebe-Bac, Powers-Bac and TB40E-Bac clones was digested with either EcoRI (lanes 1-2 and 4-6) or BgIII (lanes 8-9 and 11-13) and separated on a 0.5% agarose gel. The restriction cut and subsequent Southern Blot analyses confirmed the correct integration of the gpt-bac cassette between US1 and US6/7. In the EcoRI restriction cut a 5.9 kb band arises due to the integration of the gpt-Bac cassette. An "a" sequence polymorphism could also be confirmed which arises due to a shuffling of "a" sequences at the internal and terminal repeats during the replication of HCMV.
[0041]M: molecular weight marker 1 kb ladder.
[0042]Analyses were performed as previously described (Journal of Virology, 8320-8329, 1999).
[0043]FIGS. 5a and 5b:
[0044]DNA derived from individually grown FIX-bac-7 bacmid clones (lane 1) or FIX-bac-7 mutant bacmid clones Δ-UL/b' (lane 2), Δ-UL130-132 (lane 3), Δ-UL132 (lane 4), Δ-UL131 (lane 5), A-UL130 (lane 6), Δ-UL130K (lane 7), Δ-UL128 (lane 8), Δ-UL128K (lane 9) was digested with either EcoRI (FIG. 5a) or HindIII (FIG. 5b), respectively, and run on a 0.5% agarose gel. By probing with the pAcyc177 probe (for detection of the correct integration of the kanamycin resistance gene) the predicted bands can be detected by Southern Blot hybridization in the HindIII digest (FIG. 5b): a 6.5 kb and 4.7 kb band in Δ-UL/W (lane 2), a 6.5 kb and 1.3 kb band in Δ-UL130-132 (lane 3), a 7.5 kb and 1.3 kb band in Δ-UL132 (lane 4), a 7.0 kb and 2.2 kb band in Δ-UL131 (lane 5), a 6.0 kb and 2.8 kb band in Δ-UL130 (lane 6), a 6.0 kb and 2.8 kb band in Δ-UL130K (lane 7), a 5.2 kb and 3.6 kb band in Δ-UL128 (lane 8) and a 5.3 kb and 3.8 kb band in Δ-UL128K (lane 9).
[0045]M: molecular weight marker 1 kb ladder.
[0046]Analyses were performed as previously described (Journal of Virology, 8320-8329, 1999).
[0047]FIG. 6: shows the following sequence comparisons:
a) Comparison RACE clone1 (Bases 2 . . . 1754 of SEQ ID NO:15) to FIX genomic sequence (Bases 4803 . . . 6782 of SEQ ID NO:1);b) Race clone 3-10 (Bases 2 . . . 1882 of SEQ ID NO:7) to FIX genomic sequence (Bases 4793 . . . 6793 of SEQ ID NO:1);c) Race clone 1 (Bases 1 . . . 1777 of SEQ ID NO:15) to RACE clone 3-10 (Bases 11 . . . 1895 of SEQ ID NO:7);d) RACE clone 1, (SEQ ID NO:15), 3-10 (Bases 12 . . . 1940 of SEQ ID NO:7), 75-3 (Bases 12 . . . 1411 of SEQ ID NO:16), 72-2/4 (Bases 12 . . . 756 of SEQ ID NO:13) to FIX genomic sequence (designated VR7) (Bases 4501 . . . 7646 of SEQ ID NO:1);e) RACE clone 1 (SEQ ID NO:15), 3-4(SEQ ID NO:6), 3-10(Bases 12 . . . 1940 of SEQ ID NO:7), 75-3(Bases 12 . . . 1411 of SEQ ID NO:16), 57-5-2(SEQ ID NO:52), 57-5(Bases 12 . . . 651 of SEQ ID NO:8), 57-6(SEQ ID NO:53), 72-8(Bases 1 . . . 888 of SEQ ID NO:27), 73-8(SEQ ID NO:54), 74-5(Bases 12 . . . 686 of SEQ ID NO:18), 75-5 (SEQ ID NO:55) to Fix genomic sequence (designated VR7 (Bases 4701 . . . 6890 of SEQ ID NO:1)
[0048]FIG. 7: shows fast sequence alignment of
a) FIX7(SEQ ID NO:1)-HCU 33331(SEQ ID NO:56);
b) TB40E4(SEQ ID NO:4)-HCU 33331(SEQ ID NO:57);
c) PAN1(SEQ ID NO:2)-HCU 33331(SEQ ID NO:58);
d) TB40E4(SEQ ID NO:13)-FIX7(SEQ ID NO:1);
e) TB40E1(SEQ ID NO:3)-TB40E4(SEQ ID NO:4);
f) TB40E1(SEQ ID NO:4)-FIX7(SEQ ID NO:1);
g) PAN1(SEQ ID NO:2)-TB40E4(SEQ ID NO:4);
h) PAN1(SEQ ID NO:2)-FIX7(SEQ ID NO:1).
[0049]The sequence listing contains the following sequences:
SEQ ID NO:1 FIX7,
SEQ ID NO:2 PAN1,
SEQ ID NO:3 TB40E1,
SEQ ID NO:4 TB40E4
[0050]and the RACE sequences:
SEQ ID NO:5 Seq57-5-2-,
SEQ ID NO:6 Seq3'-4-,
SEQ ID NO:7 Seq3-10-,
SEQ ID NO:8 Seq57-5-,
SEQ ID NO:9 Seq57-6-,
SEQ ID NO:10 Seq 57-7-,
SEQ ID NO:11 Seq72-1-10-,
SEQ ID NO:12 Seq72-2-17-,
SEQ ID NO:13 Seq72-2-4-,
SEQ ID NO:14 Seq72-5-,
SEQ ID NO:15 Seqrace(1)-,
SEQ ID NO:16 Seq75-3-,
SEQ ID NO:17 Seq74-4-,
SEQ ID NO:18 Seq74-5-,
SEQ ID NO:19 Seq74-8,
SEQ ID NO:20 Seq75-1-,
SEQ ID NO:21 Seq75-4-,
SEQ ID NO:22 Seq76-7-,
SEQ ID NO:23 Seq75-5-,
SEQ ID NO:24 Seq77-14-
SEQ ID NO:25 Seq73-8-,
SEQ ID NO:26 Seq75-17-,
SEQ ID NO:27 Seq72-8,
SEQ ID NO:28 Seq74-3-.
EXAMPLE 1
Characterization of VR1814
[0051]HCMV virus strain VR1814 was isolated from cervical secretions and passaged in HEF 43 times. Before BAC cloning, VR 1814 was cultured in HUVEC for 2 months. HUVEC (human umbelical vein endothelial cell)-tropism and PMNL-tropism of VR1814 were determined by: i) propagating VR1814 in primary HUVEC cultures (Revello et al., J. Gen. Virol., submitted) and ii) coculturing purified PMNL with HUVEC infected with VR1814, following by immunologic staining of positive PMNL (Revello, J. Clin. Invest. 1998; Gema et al.) (FIG. 1A-E).
EXAMPLE 2
[0052]Cloning of the clinical HCMV isolate VR1814 as FIX (fusion inducing factor X)-Bac (bacterial artificial chromosome) in E. coli. Generation of the FIX recombinant containing the bac vector.
[0053]The HCMV recombinant virus was generated by homologous recombination in cell culture. The plasmid pEB 1997 (Borst et al., J. Virol 73, 8320-8329, 1999) was linearized with the restriction enzyme Xcml. pEB 1997 contains a tk-gpt-bac-cassette flanked with HCMV homologous sequences of US1-US2 (nt 192648 to 193360) on the right side and US6-US7 (nt 195705-197398) on the left side of the cassette. HFF cells (human forescin fibroblasts) (1×107 cells) were transfected with 35 μg of linearized plasmid pEB1997 using a Gene Pulser II (Biorad). Conditions of transfection were 960 μF, 220V. Cells were seeded in a T25 tissue culture flask and cultured overnight in DMEM supplemented with 5% FCS. After 24 h the monolayer was washed once with PBS and infected with an MOI 5 (moiety of infection) using the HUVEC grown clinical isolate VR1814 from Example 1 for 6 h. Cells were washed after infection and DMEM 5% FCS was added. Cells were cultured for 2 weeks until 100% CPE (cytopathogenic effect) was reached. Infected cells and supernatant were used to infect a new flask of a confluent monolayer of HF cells for 6 hours. Cells were washed carefully with PBS and selection medium was applied containing (100 μM xanthine and 25 μM mycophenolic acid). After 3 weeks when 100% CPE was reached, cells and supernatant were used for two successive rounds of infection and selection in tissue culture.
EXAMPLE 3
Generation of the FIX-Bac in E. coli
[0054]After three rounds of selection in tissue culture the cell monolayer was washed with ice cold PBS and cells were lysed in 1 ml TES-buffer (10 mM Tris CI pH 7.4, 10 mM EDTA pH 8.0, 0.6% SDS). To obtain circular viral intermediates a modified HIRT extraction was applied. The sticky lysate was poured into a 2 ml eppendorf vial and 0.3 ml 5 M NaCl was added and carefully mixed. After 24 h of incubation at 4° C. cellular DNA and proteins was pelleted out by centrifugation at 14.000 rpm for 30 min. The supernatant containing the circular intermediates was phenol/chloroform extracted once and subsequently precipitated in 21/2 volumes of 95% ethanol and 0.1×3 M Na-actetate (pH 5.2) for 24 h at -20° C. DNA was pelleted at 14000 rpm at 4° C. for 30 min and washed with 70% ethanol. The dry DNA pellet was resuspended in 100 destilled water and allowed to dissolve for 24 h. Twenty-five μl of viral DNA was electroporated into E. coli DH10B using a Gene Pulser II (Biorad). Conditions were 200 Ohm, 25 μF, 2.3 kV. After incubation in LB for 2 hours at 37° C., bacteria were spun for 30 sec at 6000 rpm, resuspended in 100 μl of LB medium and plated onto agar plates containing chloramphenicol. After 48 h colonies were picked and grown in liquid culture for bacmid preparation as previously described (ref 31). FIG. 1 shows the EcoRI and BgI II restriction pattern of 5 representative clones of FIX-Bac compared to WT-virus. Since the unit long (UL) and unit short (US) region of HCMV can flip relatively to each other, two isomeric forms can be observed in E. coli. Additional polymorphism is added by the number of "a" sequence repeats in the terminal and internal repeat region which vary in individual clones.
EXAMPLE 4A
Reconstitution of Infectious Virus from FIX-Bac
[0055]To recover infectious virus from FIX-Bac clones, DNA was prepared using Nucleobond columns as previously described (ref 31). 1 μg of DNA was added to 10 μl Superfect (Gibco) and 80 μl of RPMI and incubated for 30 min to allow DNA complexes to form. A subconfluent layer of MRC-5 fibroblast in a 6 well dish seeded for 24 h was serum starved for 30 min in RPMI. Medium was completely removed after 30 min and replaced with 1 ml DMEM 5% FCS over 6 well. The DNA transfection mix was diluted with 100 μl of DMEM 5% FCS and added to the cells of a 6 well. After 4 h the transfection mix was removed and 2 ml of fresh DMEM 5% FCS was added per well. After 1 week cells were split into a new flask (T25) and cultured until 100% CPE is achieved.
EXAMPLE 4B
Phenotypic Characterization of Reconstitued RV-FIX-Bac-viruses
[0056]Infectious viruses were reconstituted from transfection of FIX-Bac clones #1, #6, #7, #11 and #14 (referred to as RV-FIX-1, RV-FIX-6, RV-FIX-7, RV-FIX-11 and RV-FIX-14, respectively) in HEF cells. Reconstituted viruses (RV) were then assayed for HUVEC-tropism and PMNL-tropism as reported. All RV-FIX-Bac derived viruses retained the phenotype observed in the parental VR1814 isolate (FIG. 2).
EXAMPLE 5
Mutation
[0057]To identify the region in the FIX-Bac-7 genome responsible for microfusion induction and endothelial cell tropism, 13.8 kB of the ULb' region were removed (mutant referred to as Delta-ULb'; primers P-ULb' and P-132) using homologous recombination with a linear PCR fragment in a recombination proficient E. coli strain. A second mutant was generated which specifically deleted the beginning of ULb' region namely UL130-132 (referred to as Delta-UL130-13; primers P-132 and P-130) which is inverted in orientation in the clinical isolates as compared to the low passage isolate Toledo. The primers used for generation of the linear PCR fragments with plasmid pAcyc 177 (New England Biolabs) as a template were as follows:
TABLE-US-00001 P-ULb': (SEQ ID NO: 29) 5'-CGC TGT AGG GAT AAA TAG TGC GAT GGC GTT TGT GGG AGA ACG CAG TAG CGA TGG GTT GCG ACG TGC ACC GAT TTA TTC AAC AAA GCC ACG-3' P-130: (SEQ ID NO: 30) 5'-AAC GGC GTC AGG TCT TTG GGA CTC ATG ACG CGC GGT TTT CAA AAT TCC CTG CGC GCG CGA CGG GCG CCA GTG TTA CAA CCA ATT AAC C-3' P-132: (SEQ ID NO: 31) 5'-AAA CCA CGT CCT CGT CAC ACG TCG TTC GCG GAC ATA GCA AGA AAT CCA CGT CGC CAC ATC TCG AGA CGA TTT ATT CAA CAA AGC CAC G-3'
[0058]The mutant viruses were reconstituted in MRC-5 cells as described under Example 4a. Testing of the Delta-ULb' and Delta-UL130-132 mutants for capacity to induce microfusion or efficiently infect endothelial cells reveiled a loss of both phenotypes. Thus, the genetic region UL130-132 is inducing both microfusion and endothelial cell tropism and the deletion of the region in the clinical isolate leads to the loss of phenotype described.
[0059]A control mutant deleting the region UL45 in the genome of FIX-Bac-7 generated according to the same method (and referred to as Delta-UL45) retained the ability to induce microfusion and grow in endothelial cells. PCR primers used for generation of this mutant were:
TABLE-US-00002 P-45.1: (SEQ ID NO: 32) 5'-GCC AGT GGT ACC ACT TGA GCA TCC TGG CCA GAA GCA CGT CGG GCG TCA TCC CCG AGT CAT AGT AGC GAT TTA TTC AAC AAA GCC ACG-3' P-45.2: (SEQ ID NO: 33) 5'-ACA CAT CGC ACA CAG ACT TTA TAA ACC GTA GTT GTC GGC GCC ATC TAG ACT CAC TTT ATT GAA AGC CAG TGT TAC AAC CAA TTA ACC-3'
[0060]Thus, the capacity to induce microfusion may reflect a novel mechanism of HCMV to spread its genome from cell to cell and infect cells which do not express the as yet elusive natural receptor of HCMV. Consequently, the genetic region UL130-132 is a crucial determinant for tissue tropism and pathogenesis of HCMV.
[0061]FIG. 3 shows HindIII and BgIII restriction patterns of the FIX-Bac mutant clones in comparison to the parental clone (FIX-7).
EXAMPLE 6
[0062]As further examples for feasibility of the cloning of clinical isolates of HCMV as bacterial artificial chromosomes in E. coli, the clinical isolates Phoebe, Powers and TB40E were cloned as bacmids according to the method described above. Additionally the vaccine strains Towne-long and Towne-short were cloned as bacmids to prove that the method of bac cloning is also feasible for cloning of vaccine strains of HCMV.
[0063]Phoebe-Bac, Powers-Bac and TB40E-Bac were deposited with the Deutsche Sammlung fur Mikroorganismen and Zellkulturen (DSZM), under DSM 14358 (Phoebe-Bac), DSM 14359 (Powers-Bac) and DSM 14360 (TB40E-Bac).
[0064]Analyses of the bacmids are shown in FIG. 4.
EXAMPLE 7
Generation of FIX-bac-7 Mutants
[0065]A linear PCR fragment was generated using the kanamycin resistance gene from plasmid pAcyc177 (New England Biolabs) as a template. The primers used for generation of the linear PCR fragments have about 60 by HCMV homolgous sequence on the 5' and 3' ends, respectively, and were designed as follows:
TABLE-US-00003 Mutant D-UL130 P-130-for: (SEQ ID NO: 34) 5'-GCG CCA CAC GCC CGG AGC CTC GAG TTC AGC GTG CGG CTC TTT GCC AAC TAG CCT GCG TCA CGG CGA TTT ATT CAA CAA AGC-3' P-130-rev: (SEQ ID NO: 30) 5'-AAC GGC GTC AGG TCT TTG GGA CTC ATG ACG CGC GGT TTT CAA AAT TCC CTG CGC GCG CGA CGG GCG CCA GTG TTA CAA CCA ATT AAC C-3' Mutant D-UL130K P-130-for-kons: (SEQ ID NO: 35) 5'-CCC GGA GCC TCG AGT TCA GCG TGC GGC TCT TTG CCA ACT AGC CTG CGT CAC GGG AAA TAA TCG ATT TAT TCA ACA AAG CCA CG-3' P-130-rev: (SEQ ID NO: 30) 5'-AAC GGC GTC AGG TCT TTG GGA CTC ATG ACG CGC GGT TTT CAA AAT TCC CTG CGC GCG CGA CGG GCG CCA GTG TTA CAA CCA ATT AAC C-3' Mutant D-UL131: P-131-for: (SEQ ID NO: 36) 5'-TGT CTT TCG GTT CCA ACT CTT TCC CCG CCC CAT CAC CTC GCC TGT ACT ATG TGT CGA TTT ATT CAA CAA AGC CAC G-3' P-131-rev: (SEQ ID NO: 37) 5'-GCT AGT TGG CAA AGA GCC GCA CGC TGA ACT CGA GGC TCC GGG CGT GTG GCG GCC AGT GTT ACA ACC AAT TAA CC-3' Mutant D-132 P-132-for: (SEQ ID NO: 31) 5'-AAA CCA CGT CCT CGT CAC ACG TCG TTC GCG GAC ATA GCA AGA AAT CCA CGT CGC CAC ATC TCG AGA CGA TTT ATT CAA CAA AGC CAC G-3' P-132-rev: (SEQ ID NO: 38) 5'-ATG AGA CAT CAT ACA CAT AGT ACA GGC GAG GTG ATG GGG CGG GGA AAG AGT TGG AAC CGA AAG GCC AGT GTT ACA ACC-3' Mutant D-128 P-128-for: (SEQ ID NO: 39) 5'-GCA CCC ATC CCA ATC TCA TCG TTT GAG CCC GTC GCG CGC GCA GGG AAT TTT GAA AAC CGC GCG TCC GAT TTA TTC AAC AAA GCC ACG-3' P-128-rev: (SEQ ID NO: 40) 5'-TCG CGC GAC ATG AAT TTA GTC GGC GAC AGA AAT CTC GAA ACG CGT ATT TCG GAC AAA CAC ACA TGC CAG TGT TAC AAC CAA TTA ACC-3' Mutant D-128K P-128-for-kons: (SEQ ID NO: 41) 5'-TGC GTT CTG TGG TGC GTC TGG ATC TGT CTC TCG ACG TTT CTG ATA GCC ATG TTC CAT CGA CGA TTT ATT CAA CAA AGC CAC G-3' P-128-kons2: (SEQ ID NO: 42) 5'-CGG CAC ACA TCC AGC CGT TTG TGT TTC TTA ACG CTC TCC AGG TAC TGA TCC AGG CCC ACG GCC AGT GTT ACA ACC AAT TAA-3'
[0066]PCR was performed using the plasmid pAcyc177 as a template. FIX-bac-7 mutants were generated in a recombinant proficient E. coli strain by transformation of the respective purified PCR product into the FIX-bac-7 containing E. coli strain. The mutant clones were selected on chloramphenicol (12.5 μg/ml) and kanamycin (50 μg/ml) containing agarose plates. Subsequently, individual clones were picked and grown in Luria Bertani medium supplemented with chloramphenicol (12.5 μg/ml) and kanamycin (50 μg/ml). DNA of the resulting bacmid clones was analysed by restriction enzyme analyses and Southern Blot hybridization.
EXAMPLE 8
Determination of the PMN- and HUVEC Phenotype of the RV-FIX Mutants
[0067]All RV-FIX (reconstituted virus-FIX) mutant viruses were reconstituted from FIX-bac-7 mutant clones as previously described. Phenotypical testing for PMNL tropism and HUVEC tropism was also performed as previously described. Table 1 provides a summary of the virus mutant phenotypes. As a conclusion of phenotypical testing the mutant viruses we confer that PMNL tropism and induction of microfusion events is encoded within the genetic region spanning UL131-UL128 genes and HUVEC tropism is encoded within the genetic region of UL-132-128 genes. Disruption of the genes UL131-128 abrogates both HUVEC and PMN tropism phenotype and consequently the genetic region between UL131 and UL128 is essentially required for PMNL tropism and induction of microfusion events of clinical HCMV isolates. Additionally UL132 gene is contributing to the HUVEC phenotype of clinical isolates of HCMV. Taken together we have identified a genetic region (UL132-128) within clinical isolates of HCMV which encodes important pathogenicity features of clinical isolates. The same region may also provide important pathogenicity factors for growth of clinical isolates in other cell types like dendritic cells, monocytes, macrophages, stem cells and may confer the resistance of clinical isolates of HCMV to NK cell recognition by coding for chemokine-like or cytokine-like factors. The genetic region of UL132-128 identified in FIX-bac-7 is therefore an important target for drug design, gene therapy and vaccine development against HCMV. We expect that the transfer of the UL132-128 genetic region of FIX-bac into the laboratory strain AD169 will confer HUVEC tropism, PMNL tropism and microfusion phenotype characteristics to the fibroblast adapted AD169 laboratory strain or any other virus strain.
TABLE-US-00004 TABLE 1 Testing of PMNL-and HUVEC-tropism of RV-FIX mutant viruses experiment 1a experiment 2 PMNL-tropism HUVEC-tropism RV-FIX WT positive growth on HUVEC RV-FIX D-UL/b' negative no growth at passage 4 RV-FIX D-UL130 negative no growth at passage 4 RV-FIX D-UL131 negative no growth at passage 4 RV-FIX D-UL132 positive no growth at passage 4 RV-FIX D- negative no growth at passage 4 UL130-132 RV-FIX D-UL130K negative no growth at passage 4 RV-FIX D-UL128 negative no growth at passage 4 RV-FIX D-UL128K negative no growth at passage 4 RV-FIX D-UL45 positive growth on HUVEC aTwo independent experiments are shown.
EXAMPLE 9
Transcript Mapping and Sequencing of the FIX-bac UL/b' Region
[0068]For mapping of the transcripts spanning the UL132-128 region 5' RACE (rapid amplification of cDNA ends) and 3' RACE procedures were performed using the Clontech SMART® RACE cDNA Amplification kit according to the manufacturers' instructions. RNA was generated from RV-FIX infected fibroblasts (MOI 0.1) at day 7 p.i. using the Qiagen RNA extraction and mRNA purification kits.
[0069]Gene Specific RACE Primers were as follows:
[0070]For rapid amplification of cDNA ends (RACE) from the 5' RACE cDNA sample the following primers were used:
TABLE-US-00005 Primer 57-GSP1: (SEQ ID NO: 43) 5'-CGG CAC ACA TCC AGC CGT TTG TGT TTC TTA 3' Primer 72-GSP2-5'RACE-1: (SEQ ID NO: 44) 5'-TAA CGC TCT CCA GGT ACT GAT CCA GGC CCA-3' Primer 73-GSP-5'RACE-2: (SEQ ID NO: 45) 5'-TCG TCA GTT TGT TGT GTA CGA CCT GGC GTG-3' Primer 74-GSP2-5'RACE-3: (SEQ ID NO: 46) 5'-TAT TGG CCT CGG TGA ACG TCA ATC GCA CCT-3'
[0071]For rapid amplification of cDNA ends (RACE) from the 3' RACE cDNA sample the following primers were used:
TABLE-US-00006 Primer 56-GSP2: (SEQ ID NO: 47) 5'-TGT GTC GGG TGT GGC TGT CTG TTT GTC TGT-3' Primer 75-GSP2-3'RACE-1: (SEQ ID NO: 48) 5'-TCT GCT TCG TCA CCA CTT TCA CTG CCT GCT-3' Primer 76-GSP2-3'RACE-2: (SEQ ID NO: 49) 5'-CGC AGA AGA ATG TTG CGA ATT CAT AAA CGT-3' Primer 77-GSP2-3'RACE-3: (SEQ ID NO: 50) 5'-GCT GCG GTG TCC GGA CGG CGA AGT CTG CTA-3' Primer 78-GSP2-3'RACE-4: (SEQ ID NO: 51) 5'-CCA GCT GGC AGA TTC CCA AAC TAA TGA AAG-3'.
[0072]PCR products were subsequently cloned into pT-Adv vector using the AdvanTAge®PCR Cloning Kit (Clontech) according to the manufacturers' guidance. Individual clones were screened for cDNA inserts by DNA preparation and EcoRI restriction cut. Insert containing clones were sequenced using M13 sequencing primers. The respective sequences of the 3'RACE and 5'RACE clones are attached as individual sequencing files: Clones RACE1, 3-4, 3-10, 57-5-2, 57-5, 57-6, 57-7, 72-1-10, 72-2-4, 72-2-17, 72-5, 72-8, 73-8, 74-3, 74-4, 74-5, 74-8, 75-1, 75-3, 75-4, 75-5, 75-17, 76-7, 77-14.
[0073]A comparison of the FIX-Bac genomic sequence (designated VR) and individual RACE clones is depicted in FIG. 6:
a) Comparison RACE clone1 to FIX genomic sequence;b) RACE clone 3-10 to FIX genomic sequence;c) RACE clone 1 to RACE clone 3-10;d) RACE clone 1, 3-10, 75-3, 72-2/4 to FIX genomic sequence (designated VR7);e) RACE clone 1, 3-4, 3-10, 75-3, 57-5-2, 57-5, 57-6, 72-8, 73-8, 74-5, 75-5 to FIX genomic sequence (designated VR7)
[0074]The genomic sequence of the UL/b' region of a clinical bacmid clone PAN1 is attached as sequence file (Seq Id No. 2). Parts of the genomic sequence of the UL/b' region of FIX7-Bac (Seq Id No. 1), TB40E1-Bac (Seq Id No. 3) and TB40-E4-Bac (Seq Id No. 4) were also determined and are attached as sequencing files. In FIG. 7 the genomic sequences of PAN-Bac, FIX-Bac and TB40E-Bac were compared in a sequence alignment to the published genomic sequence of Toledo (gb:HCU 33331) and to each other using DNAman software: Fast sequence alignment of
a) FIX7(SEQ ID NO:1)-HCU 33331(SEQ ID NO:56);
b) TB40E4(SEQ ID NO:4)-HCU 33331(SEQ ID NO:57);
c) PAN1(SEQ ID NO:2)-HCU 33331(SEQ ID NO:58);
d) TB40E4(SEQ ID NO:13)-FIX7(SEQ ID NO:1);
e) TB40E1(SEQ ID NO:3)-TB40E4(SEQ ID NO:4);
f) TB40E1(SEQ ID NO:4)-FIX7(SEQ ID NO:1);
g) PAN1(SEQ ID NO:2)-TB40E4(SEQ ID NO:4);
h) PAN1(SEQ ID NO:2)-FIX7(SEQ ID NO:1).
[0075]In summary, our RACE PCR analyses have identified several novel transcripts within the UL132 to UL128 region of FIX-bac. Two transcripts (RACE clone 3-10, RACE clone1 and RACE clone 3'-4) are of particular interest. They show that one major transcript of about 2.0 kb is covering the whole UL131-128 region (see FIGS. 6a-c). RACE clone1, RACE clone 3'-4 and RACE clone 3-10 have a ployA tail and are spliced at the 3' end (position 1721 nt to 1845 nt referred to FIG. 6e). Both, RACE clone 1 and RACE clone 3'-4 have an additional splice at the 5' end (position 331 nt to 440 nt referred to FIG. 6e). The ATG start codon of these transcripts is at position nt 96 to nt 98 referred to FIG. 6e). The predicted 5' end of these three transcripts is presumably 10-50 by upstream of the sequenced end of the clones (nt 50 to nt 100 referred to FIG. 6e). 5' ends of other transcripts in the UL131-128 region are shown in FIG. 6d-e) and could be mapped to nt 641 in clone 75-5; nt 717 in clone 57-5-2; nt 783 in clone 57-5; nt 438 in clone 74-5; nt 970 in clone 73-8 and nt 1150 in clone 72-8.
[0076]Since it was shown that the genetic region of UL132 to UL128 is the genetic determinant for induction of microfusion, HUVEC and PMN tropism, the identified transcripts running through this region are candidates for therapeutic intervention, drug design, vaccine development, attenuation of virus virulence, spread and antigenicity of the virus, latency and reactivation as well as immunological control of HCMV by immune cells (NK cells, T-cells, B-cells, dendritic cells, endothelial cells and monocytes, macrophages, hematopoietic precursors and stem cells). Ectopic transfer of the genetic region UL132-128 of FIX-Bac-7 or the respective identified cDNAs into a fibroblast adapted HCMV virus (for example AD 169) will confer microfusion characteristics, cell to cell spread of virus material, HUVEC and PMNL tropism and possibly other pathogenicity features to the respective virus.
REFERENCES
[0077]1. Mocarski, E. S. 1996, Cytomegaloviruses and their replication. p. 2447-2492 in B. N. Fields, D. M. Knipe and P. M. Howley. Fields Virology 3rd edition Lippincott-Raven Publishers, Philadelphia, Pa. [0078]2. Revello, G. M. at al. 1999, Quantification of Human Cytomegalovirus DNA in Amniotic Fluid of Mothers of Congenitally Infected Fetuses in Journal of Clinical Microbiology, Vol. 37, No. 10, 3350-3352 [0079]3. Revello, G. M. at al. 1999, Prenatal Diagnostic and Prognostic Value of Human Cytomegalovirus Load and IgM Antibody Response. in Blood of Congenitally Infected Fetuses in The Journal of Infectious Diseases, 180:1320-3 [0080]4. Brown J. M., Kaneshima H., Mocarski E. S. 1995, Dramatic Interstrain Differences in the Replication of Human Cytomegalovirus in SCID-hu mice, in The Journal of Infectious Diseases 171(6):1599-603 [0081]5. 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Sequence CWU
1
5817646DNAHuman cytomegalovirus 1actgtggcta gaaactggtt acctgtgaag
atggctgact atcctgttgt gtcctggaaa 60agctttcagc gtcgtaggtg gactttgcag
tatgcgggtt agtgaagtta tgtcatttat 120ttacgtttac gatctcgtat tacaaaccgc
ggagaggatg ataccgttcg gccccatgag 180ttatttttat tcttccggta ggaggcatga
agcctctggt gatgcttatt ttgctgagta 240tgctattggc atgcataggg aaaactgaaa
tatgcaaacc cgaagaagtg caattaggaa 300atcagtgttg tcccccatgt aaacaaggat
atcgtgttac aggacaatgt acgcaatata 360cgagtacaac atgtacactt tgccctaacg
gtacgtatgt atcagggctt tacaattgta 420ccaattgcac tgagtgtaat gacactgagg
ttacaattcg taactgcact tccactaata 480acaccgtatg cgcatctaag aattatacgt
cgttgtccgt tccaggcgtc caacatcata 540agcaacgaca aaatcatacc gcacatgtaa
ccgtcaaaca agggaaaagt ggtcgtcata 600ctctagcctg gttgtccctc ttcatctttc
tcgtgggtat catactttta attctctatc 660ttatagccgc ctatcggagt gagagatgcc
aacagtgttg ctcaatcggc aaaattttct 720accgcaccct gtaagcttcc tgttgttgtt
tttacatcac ggtgcgatga agtcacacag 780ataattacag atgagctgtt catatttttt
attatttttt ccaattcctg cactaaaaaa 840agaagcactt tacggaaccg tgtctgaata
tctgtgggga atttaggtac tttttgccga 900cgtcaggaaa aataagctgt cgcctacata
agagcccggt gctatcgtgc tgtcactctt 960tcttgttgcc ttcgatgtac ggcgtcctgg
ctcattacta ctccttcatc agtagcccca 1020gcgttatggt taattttaaa catcataacg
ccgtgcagct gttgtgtgca cggacccgag 1080acggcactgc cggatgggaa cgtttaaccc
atcatgcgtc gtatcacgcg aactatgggg 1140catacgccgt gttgatggct acatcgcaaa
gaaagtccct agtgttacat cgatacagtg 1200ccgtgacagc cgtggccctg cagctcatgc
ctgttgagat gctccgtaag ctagatcagt 1260cggactgggt acggggtgcc tggatcgtgt
cagagacttt tccaaccagc gaccccaaag 1320gattttggag cgacgatgac tcctcgatgg
gtggaagtga tgattgatga tgagaacctg 1380acaagaaaga cgagagagaa attcagagct
gtcattgtag aattagtcta gattcctgat 1440aataaacggt atcgattttg aaacctaatt
gacgtgtgat cgatttttaa acctgtgtgt 1500tgtgtgattg attggtatgt ggggggatcc
gatttcaaag gggggtactt atcgggaatt 1560gatgtgtcat ggacgcagtt ttgagtgatt
ttccgggaat accggatatt acgaattgat 1620gtaagttacg tcagtaatta agtcaggatg
cggtttattt tcggtttgct gattggtctt 1680gtaatcgtgt atacgtatta ttatgaagta
caaagtacgg aactacgttg cccatgcact 1740aatggtttac acgatccttt atatggcata
ttttatgctg gtcgtgaccc tccacgtcct 1800cccggttgtg aaaaagatca atattattta
aaacctccca aaggtaaagc tgtatgctta 1860ggtccacatc atcatttatc aatatggctc
aatggtcaaa atagtagttt atggcacaaa 1920gtgctggtga cgggaaaaaa cggtaatgga
ccacacgtaa ctaagaaagg tgactttcct 1980agaggtcgaa aaaatataat gatttagctt
aatatggata tatacgatag ctgataaatt 2040ttccacgaaa aaggataacg caatatgttt
ttgatatggt gctaacatgg ttacatcatt 2100cgattataaa ctcgcatatc aaacttttat
cggtaccaca cctgtcattg accgcatata 2160tgttatttac cgtgtgtttc ccggtccatc
ttttagaatt ggaagattac gacaggcgtt 2220gtcgttgtaa caaccaaatt ctgttgaata
ccctgccggt cggaactcaa ctgcttaagc 2280caatcgcagc gagcgaaagc tgcaatcgtc
aggaagtgct ggctatttta aaggacaaag 2340gaaccaagtg tctcaatcct aacgcgcaag
ccgtgcgtcg tcacatcaac cggctatttt 2400ttcggttaat cttagacgag gaacaacgca
tttacgacgt agtgtctacc aatattgagt 2460tcggtgcctg gccagtccct acggcctaca
aagcctttct ctggaaatac gccaagaaac 2520ttaattacca ctactttaga ctgcgttggt
gatcatgtcc ctattttacc gtgcggtagc 2580cctgggcacg ctgagcgctc tggtgtggta
tagcactagt atcctggcag agattaacga 2640agaatcctgc tcctcatctt ctgtggacca
cgaagactgc gaggaaccgg acgagatcgt 2700tcgcgaagag caagactatc gggctctgct
ggccttttcc ctagtgattt gcggtacgct 2760cctcgtcact tgtgtgatct gagacgtcat
gctggtagcg tttatgagtc gggcggtggc 2820cggcacgccg catttcctaa cccgcgcagc
atgttgcgct tgctgttcac gctcgtccta 2880ctggccctcc acgggccgtc tgtcaacgct
agccgcgact atgtgcatgt tcggctactg 2940agctaccgag gcgaccccct ggtcttcaag
cacacttttt cgggtgtgcg tcgacccttc 3000accgagctag gctgggctgt gtgtcgcgac
tgggacagta tgcattgcac gcctttctgg 3060tctaccgatc tggagcagat gaccgactcg
gtgcgacgtt acagcacggt gagccccggc 3120aaggaagtga cgcttcagct tcacgggaac
caaaccgtac agccgtcgtt tctaagcttt 3180acgtgccgcc tgcagctaga acccgtggtg
gaaaatgttg gcctctacgt ggcctacgtg 3240gtcaacgacg gtgaacgccc acagcagttt
tttacaccgc aagtagacgt ggtacgcttt 3300gctctatatc tagaaacgct ctcccggatc
gtggaaccgt tagaatcagg tcgcctggca 3360gtggaatttg atacgcctga cctagctctg
gcgcccgatt tagtaagcag cctcttcgtg 3420gccggacacg gcgagaccga cttttacatg
aactggacgc tgcgtcgcag tcagacccac 3480tacctggagg agatggcctt acaggtggag
attctaaagc cccgcggcgt acgtcaccgc 3540gctattatcc accatcctaa gctacagccg
ggcgttggcc tgtggataga tttctgcgtg 3600taccgctaca acgcgcgcct gacccgcggc
tacgtacgat acaccctgtc accgaaagcg 3660cgcttgcccg caaaagcaga gggttggctg
gtgtcactag acagattcat cgtgcagtac 3720ctcaacacat tgctgattac aatgatggcg
gcgatatggg ctcgcgtttt gataacctac 3780ctggtgtcgc ggcgtcggta gaggcttgcg
gaaaccacgt cctcgtcaca cgtcgttcgc 3840ggacatagca agaaattcac gtcgccacgt
ctcgagaatg ccggccccgc ggggtcccct 3900tcgcgcaaca ttcctggccc tggtcgcgtt
cggattgctg tttcagatag acctcagcga 3960cgctacaaat gtgaccaaca gcacaaacgt
ccctactagc accagcagca gaaatagcgt 4020cgacaacgcc acgagtagcg gacccacgac
cgggatcaac atgaccacca cccacgagtc 4080ttccgttcac aacgtgcgca atgacaaaat
catgaaagtg ctggctatcc tcttctacat 4140cgtgacaggc acctccattt tcagcttcat
agcggtactc atcgcggtag tttactcctc 4200gtgttgcaag cacccgggcc gctttcgttt
cgccgacgaa gaagccgtca atctgttgga 4260cgacacggac gacagtggcg gcagcagccc
gtttggcagc ggttcccgac gaggttctca 4320gatccccgcc ggattttgtt cctcgagccc
ttatcagcgg ttggaaactc gggactggga 4380cgaggaggag gaggcgtccg cggcccgcga
gcgcatgaaa catgatcctg agaacgtcat 4440ctatttcaga aaggatggca acttggacac
gtcgttcgtg aatcccaatt atgggagagg 4500ctcgcctttg accatcgaat ctcacctctc
ggacaatgag gaggacccca tcaggtacta 4560cgtctcggtg tacgatgaac tgaccgcctc
ggaaatggaa gaaccttcca acagcaccag 4620ctggcagatt cccaaactaa tgaaagttgc
tacgcaaccc gtctcgctca gagatcccga 4680gtacgactag gctttttttt ttgtctttcg
gttccaactc tttccccgcc ccatcacctc 4740gcctatacta tgtgtatgat gtctcataat
aaagctctct ttctcagtct gcaacatgcg 4800gctgtgtcgg gtgtggctgt ctgtttgtct
gtgcgccgtg gtgctgggtc agtgccagcg 4860ggagaccgca gaaaaaaacg attattaccg
agtaccgcat tactgggacg cgtgctctcg 4920cgcgctgcct gaccaaaccc gttacaagta
tgtggaacag ctcgtggacc tcacgttgaa 4980ctaccactac gatgcgagcc acggcttgga
caactttgac gtgctcaaga ggtgagggta 5040cgcgctaaag gtgtatgaca acgggaaggt
aagggcgaac gggtaacggg taggtaaccg 5100catggggtgt gaaatgacgt tcggaacctg
tgcttgcaga atcaacgtga ccgaggtgtc 5160gttgctcatc agcgacttta gacgtcagaa
ccgtcgcggc ggcaccaaca aaaggaccac 5220gttcaacgcc gccggttcgc tggcgcctca
cgcccggagc ctcgagttca gcgtgcggct 5280ctttgccaac tagcctgcgt cacgggaaat
aatatgctac ggcttctgct tcgtcaccac 5340tttcactgcc tgcttctgtg cgcggtttgg
gcaacgccct gtctggcgtc tccgtggttc 5400acgctaacgg cgaaccagaa tccgtccccg
ccatggtcta aactgacgta tcccaaaccg 5460catgacgcgg cgacgtttta ctgtcctttt
ctctatccct cgcccccacg gtccccctcg 5520caattcccgg ggttccagcg ggtatcaacg
ggtcccgagt gtcgcaacga gaccctgtat 5580ctgctgtaca accgggaagg ccagaccttg
gtggagagaa gctccacctg ggtgaaaaag 5640gtgatctggt atctgagcgg tcgcaatcag
accatcctcc aacggatgcc ccgaacggct 5700tcgaaaccga gcgacggaaa cgtgcagatc
agcgtggaag acgccaagat ttttggagcg 5760cacatggtgc ccaagcagac caagctgcta
cgcttcgtcg tcaacgatgg cacgcgttat 5820cagatgtgtg tgatgaagct ggagagctgg
gcccacgtct tccgggacta cagcgtgtct 5880tttcaggtgc gattgacgtt caccgaggcc
aataaccaga cttacacctt ctgtacccat 5940cccaatctca tcgtttgagc ccgtcgcgcg
cgcagggaat tttgaaaacc gcgcgtcatg 6000agtcccaaag acctgacgcc gttcttgacg
acgttgtggc tgctattggg tcacagccgc 6060gtgccgcggg tgcgcgcaga agaatgttgc
gaattcataa acgtcaacca cccgccggaa 6120cgctgttacg atttcaaaat gtgcaatcgc
ttcaccgtcg cgtacgtatt tttatgattg 6180tctgcgttct gtggtgcgtc tggatttgtc
tctcgacgtt tctgatagcc atgttccatc 6240gacgatcctc gggaatgcca gagtagattt
tcatgaatcc acaggctgcg gtgtccggac 6300ggcgaagtct gctacagtcc cgagaaaacg
gctgagattc gcgggatcgt caccaccatg 6360acccattcat tgacacgcca ggtcgtacac
aacaaactga cgagctgcaa ctacaatccg 6420taagtctctt cctcgagggc cttacagcct
atgggaaagt aagacagagg gacaaaacat 6480cattaaaaaa aaagtctaat ttcacgtttt
gtaccccccc ttcccctccg tgttgtaggt 6540tatacctcga agctgacggg cgaatacgct
gcggcaaagt gaacgacaag gcgcagtacc 6600tgctgggcgc cgctggcagc gttccctatc
gatggatcaa cctggaatac gacaagataa 6660cccggatcgt gggcctggat cagtacctgg
agagcgttaa aaaacacaaa cggctggatg 6720tgtgccgcgc taaaatgggc tatatgctgc
agtgaataat aaaatgtgtg tttgtccgaa 6780atacgcgttt tgagatttct gtcgccgact
aaattcatgt cgcgcgatag tggtgtttat 6840cgccgataga gatggcgata ttggaaaaat
cgatatttga aaatatggca tattgaaaat 6900gtcgccgatg tgagtttctg tgtaactgat
atcgccattt ttccaaaagt gatttttggg 6960catacgcgat atctggcgat agcgcttata
tcgtttacgg gggatggcga tagacgactt 7020tggtgacttg ggcgattctg tgtgtcgcaa
atatcgcagt ttcgatatag gtgacagacg 7080atatgaggct atatcgccga tagaggcgac
atcaagctgg cacatggcca atgcatatcg 7140atctatacat tgaatcaata ttggccatta
gccatattat tcattggtta tatagcataa 7200atcaatattg gctattggcc attgcatacg
ttgtatccat atcataatat gtacatttat 7260attggctcat gtccaacatt accgccatgt
tgacattgat tattgactag ttattaatag 7320taatcaatta cggggtcatt agttcatagc
ccatatatgg agttccgcgt tacataactt 7380acggtaaatg gcccgcctgg ctgaccgccc
aacgaccccc gcccattgac gtcaataatg 7440acgtatgttc ccatagtaac gccaataggg
actttccatt gacgtcaatg ggtggagtat 7500ttacggtaaa ctgcccactt ggcagtacat
caagtgtatc atatgccaag tacgccccct 7560attgacgtca atgacggtaa atggcccgcc
tggcattatg cccagtacat gaccttatgg 7620gactttccta ctggcagtac atctac
7646216570DNAHuman cytomegalovirus
2ttttcgggac ggtcggttaa cgtgggtttc aggggaaagc tgtaagcacg ggaaaggagc
60gctgataggc gaggcaacgc acgaaggtcc aagcggcggc ggcgccgact tccaccatca
120ggccaacgac cagcatccgc agcagcagcg cccaggcgat ctcgcgctcg acgacggcta
180cggcgacgag gcagaacatc tcaacccaga cgacaagcgc caggaggtag agcacggccg
240gaaagaccgc gggcgttaac atctagtcgc ggagaaggaa acaaaaacgg ttgaaaacgg
300ggactgcgga gttgctttgt tcaggagacg acgacgggag cgaacgggat ggcgctggat
360acgctagcgg ggctggctat ctgcgtgggt ctagtcatgg gtgtcaccgt gatcgcgtcg
420tgcgcgctgc tggtgtttta ttattgcgat gagagagggg atggccgtcc gtcgaagctg
480ttgcaacgta gcattcgacg ttggcgacac ggccttagca ccgaatcctt aaccgctatc
540ctgccggacg gttcgtccac ggagcagaag atctaccaca cgcgacttta agtcgcggag
600gaagttacgt gggtaggagg gcaccgtgcc ccgaggcggc gacgggctag cgtataacaa
660gccgcgcgac atcgggcgag cggcggtgag acagacgcgg gcacgtcggt ggcgatagcc
720atgagttcca gcaacaatct cgatccctgg attcccgtgt gcgtcgtggt agtcatgacc
780tccgtagtcc tgttcgcagg tctgcacgtg tacctgtggt acgttcggcg gcagctggtg
840gcgttctgcc tggagaaggt gtgcgtccgc tgctgcggta aagatgagac gacgccgctg
900gtggaggatg ccaaccgccg gccgagctgg agatggtgga agtgtcagac gagcgttact
960aggagatcgc cgcggccgat gggcgccggc ggacgtgact cggcagccgc tgtagggata
1020aatagtgcga tggcgtttgt gggagaacgc agtagcgatg ggttgcgacg tgcacgatcc
1080ttcgtggcaa tgccaatggg gcgttcccac gattattgtg gcctggatag catgcgcggc
1140cctgggaatt tggtgtttgg cgggatggtc gtcgaatttg tcttctggag ccggcattgc
1200agccgtggtc ggctgttctg ttttcatgat tttcctttgc gcgtacctca tccgttaccg
1260ggaattcttt aaagactccg taatcgacct cctcacctgc cgatgggttc gctactgcag
1320ctgcagctgc aagtgcagct gcaaatgcat ctcgggcccc tgcagccgct gctgttcagc
1380gtgttacaaa gagacgatga tttacgacat ggtccaatac ggtcatcgac ggcgtcccgg
1440acacggcgac gatcccgaca gggtgatctg cgagatagtg gaaagtcccc cggtttcggc
1500gccgacggtg tccgtccccc cgccgtcgga ggagtcccac cagcccgtca tcccaccgca
1560gccgccagca ccgacatcgg aacccaaacc gaagaaaggt agggcgaaag ataaaccgaa
1620gggtagaccg aaggacaaac ctccgtgtga accgacggtg agtccacaac caccgtcgca
1680gccgacggcg atgcccggcg gtccgcccga cacgcctccc cccgccatgc cgcagatgcc
1740acccggcgta gccgaggcgg tacaagctgc cgtgcaggcg gccgtggccg cgactctaca
1800acaacaacag cagcagcatc agaccggaac gtaacccgcc cccggtgtga tgaggaattt
1860tccgacttgg cccacatctc cttcctcagt gtttggacaa taaacacatt ccttgccaaa
1920aaatgacgtt tccagaaatc caaggcataa atgtccgtac accggccctt cccgacacgg
1980agtttgagat tccaagcagg agagaagatc atggtgtgga tatggctcgg cgtcgggctc
2040ctcggcggta ccggactggc ttccctggtc ctggccattt ccttatttac ccagcgccga
2100ggccgcaagc gatccgacga gacttcgtcg cgaggccggc tcccgggtgc tgcttctgat
2160aagcgtggtg cctgcgcgtg ctgctatcga aatccgaaag aagacgtcgt cgagccgctg
2220gatctggaac tggggctcat gcgggtggcc acccacccgc cgacgccgca ggtgccgcgg
2280tgtacgtcgc tctacatagg agaggatggt ctgccgatag ataaacccga gtttcctccg
2340gcgcggttcg aaatccccga cgtatccacg ccgggaacgc cgaccagcat cggccgatct
2400ccgtcgcatt gctcctcgtt gagctctttg tcgtcttcga ccagcgtcga cacggtgctg
2460catcagccgc cgccatcctg gaagccacct ccgccgcccg agcgcaagaa gcggccgcct
2520acgccgccgg tccgggcccc caccacgcgg ctgtcgtcgc acaggccccc gacgccgata
2580cccgcgccgc gtaagaacct gagcacgccg cccatcaaga aaacaccgcc gcccacgaaa
2640cccaagccgg tcggctggac accgccggtg acacccaggc ccttcccgaa aacgccgacg
2700ccacaaaagc cgccgcggaa tccgagacta ccacgcaccg tcggtctgga gaatctctcg
2760aaagtgggac tctcgtgtcc ctgtccccga ccccgcacgc cgacggagcc gaccacgctg
2820cctatcgtgt cggtttccga gttagccccg cctcctcgat ggtcggacat cgaggaactc
2880ttggaaaagg cggtgcagag cgtcatgaag gacgctgagt ctatgcagat gacctgagac
2940cgaaggagcg agcgcgtccg ttgtacagtt gtatagcagc acacgccttc cctctttttc
3000accgcagcta agagagagaa agagagtatg tcagtcaagg gcgtggagat gccagaaatg
3060acgtgggact tggacgttgg aaataaatgg cggcgtcgaa aggccctgag tcgcattcac
3120cggttctggg aatgtcggct acgggtgtgg tggctgagtg acgccggcgt aagagaaacc
3180gacccaccgc gtccccgacg ccgcccgact tggatgaccg cggtgtttca cgttatctgt
3240gccgttttgc ttacgcttat gattatggcc atcggcgcgc tcatcgcgta cttaagatat
3300tatcaccagg acagttggcg agacatgctc cacgatctat tttgcggctg tcattatccc
3360gagaagtgcc gtcggcacca cgagcggcag agaaggagac ggcgagccat ggatgtgccc
3420gacccggaac tcggcgaccc ggcccgccgg ccgttgaacg aagctatgta ctacggcagc
3480ggctgtcgct tcgacacggt ggaaatggtg gacgagacga gacccgcgcc gccggcgctg
3540tcgtcgcccg aaaccggcga cgatagcaac gacgacgcgg ttgccggcgg aggtgctggc
3600ggggtaacat cacccgcgac tcgtacgacg tcgccgaacg cgctgctgcc ggaatggatg
3660gatgcggtgc atgtggcggt ccaagccgcc gttcaagcga ccgtgcaagt aagtggcccg
3720cgggagaacg ccgtatctcc cgctacgtaa gagggttgag ggggccgttc ccgcgcgagt
3780gctgtacaaa agagagagac tgggacgtag atccggacag aggacggtca ccatggacga
3840tctgccgctg aatgtcgggt tacccatcat cggcgtgatg ctcgtgctga tcgtggccat
3900cctctgctat ctggcttacc actggcacga caccttcaaa ctagtgcgca tgtttctgag
3960ctaccgctgg ctgatccgct gttgcgagct gtacggggag tacgagcgcc ggttcgcgga
4020cctgtcgtct ctgggcctcg gcgccgtacg gcgggagtcg gacagacgat accgtttctc
4080cgaacggccc gacgagatct tggtccgttg ggaggaagtg tcttcccagt gcagctacgc
4140gtcgtcgcgg ataacagacc gccgcgcggg ttcatcgtct tcgtcgtcgg tccacgtcgc
4200tagccagaga aacagcgtgc ctccgccgga catggcggtg acggcgccgc tgaccgacgt
4260cgatctgttg aaacccgtga cgggatccgc gacgcagttc accaccgtag ccatggtaca
4320ttatcatcaa gagtacacgt gaatgagaaa aagaaaaaag aggggagcgg atcgcgataa
4380tgtcgctttg acattctctg ctcgatctac tcagcgtctg cacgaaacgg cgtccgcacg
4440gaggcgagcc caagcgtatc tgcagcaagc ggttctttct ctcggtgatg gtggcagcat
4500cggtggcggg agcttgttcg gacgatggac ggtgaggagt ccctggcgat caggcggctc
4560ccgggtgtgg agttcaacgg gtggtaatgg tggcggtgat cggtgttaga aaacggtggc
4620cctggcaaac atatatctac tgtaaatcct ctgctctgtt aataaaaagc acacttttca
4680catgagttcg taattttatt gtgtagtgga aatttttacg tcattgggaa accccagaat
4740gaaagagtat aatgtgcaca tcaccgggag ttccctgtca gtacgaatgt acacaacgcg
4800ggttacatta cgataaactt tccggtaaaa caatgccgat acagcgtgta taacgctgat
4860tgttacgaca aacgggttcg tatatcaatt atatagtaac ggacatgctg tggatactag
4920ctttacttgc gcttaccgcg acagcgagtg agactactac aggcaccagt tctaattcca
4980gtacttccac caatagcagc aacagtactg tagcaccaac cacgccatca gtagcatgcg
5040ttcaagcttt tggcggcagt aattggacat ttccacagct cgcgctgctt gccgctagcg
5100gctggacatt atctggactc cttctcttat ttacctgctg cttttgctgc ttttggctag
5160tacgtaaaat ctgcagctgc tgcggcaact cctccgagtc agagagcaaa acaacccacg
5220cgtacaccaa tgccgcattc acttcttccg acgcgacgct acccatgggc actacagggt
5280cgtacactcc cccacaggac ggctcatttc cacctccgcc tcggtgacac agggtaaacc
5340gaaaccaacg ttgaatctga cgcggtttcg gaaagcctga gacgtcactt tcacaatgac
5400gttcgtagac acgttgatca taaaacaccg tagaggctaa ggcttcggta gggagacacc
5460tcaactgttc ctgatgagca cccgcgctct catctcttca gacttgtcat gacccccgct
5520cagactaacg ccactaccac cgtgcacccg cacgacgcaa aaaacggcag cggcggtagt
5580gccctgccga ccctcgtcgt tttcggcttc atcgttacgc tacttttctt tctctttatg
5640ctctactttt ggaacaacga cgtgttccgt aagctgctcc gctgcgcttg gatccagcgc
5700tgctgcgacc gcttcgacgc gtggcaagac gaggtcatct accgtcgtcc atcacgtcgt
5760tcccaaagcg acgacgagag tcgtactaac agcgtgtcat cgtacgttct tttatcaccc
5820gcgtccgatg gcagttttga caacccggca ctgacagaag ccgtcgacag cgtggacgac
5880tgggcgacca cctcggtttt ttacgccacg tccgacgaaa cggcggacac cgagcgccga
5940gattcgcagc aactgctcat cgagcttccg ccggagccgc tcccgcccga tgtggtagcg
6000gccatgcaga aagcggtgaa acgcgctgta cagaacgcgc tgcgccacag ccacgactct
6060tggcagcttc atcagaccct gtgacgcaga tgaacgttcc ttcttaaaca tccgaggtag
6120caatgagaca ggtcgcgtac cgccggcgac gcgagagttc ctgcgcggtg ctggtccacc
6180acgtcggccg cgacggcgac ggcgaggagg aggcagcaaa aaagacctgc aaaaaaaccg
6240gacgctcagt tgcgggcatc ccgggcgaga agctgcgtcg cacggtggtc accaccacgc
6300cggcccgacg tttgagcggc cgacacacgg agcaggagca ggcgggcagc gtctctgtga
6360aaaagggaag aaaagaatca tcatgtgccg cggggagtcg ctccgaactc tgccgtggct
6420gttctgggcg ctgttgagct gcccgcgact cctcgaatat tcttcctctt cgttcccctt
6480cgccaccgct gacatcgccg aaaagatgtg ggccgagaac tatgagacca cgtcgccggc
6540gccggtgttg gtcgccgagg gagagcaagt taccatcccc tgcacggtca tgacacactc
6600ctggcccatg gtttccattc gcgcacgttt ctgtcgttcc cacgacggta gcgacgagct
6660catcctggac gccgtcaaag gccatcggct gatgaacgga ctccagtacc gcctgccgta
6720cgccacttgg aatttctcgc agttgcatct cggccaaata ttctcgctta cttttaacgt
6780atcgatggac acggccggca tgtacgagtg cgtgctgcgc aattacagcc acggcctcat
6840catgcaacgc tttgtaattc tcacgcagct ggagacgctc agccggcccg atgaaccttg
6900ttgcacaccg gcgttaggtc gctactcgtt gggagaccag atctggtcgc cgacgccctg
6960gcgtctacgg aatcacgact gcggaacgta ccgcggcttt caacgcaact acttctatat
7020cggccgcgcc gacgccgagg attgctggaa acccgcatgt ccggacgagg aacccgaccg
7080ctgttggaca gtgatacagc gttaccggct ccccggcgac tgctaccgtt cgcagccaca
7140cccgccgaaa tttttaccgg tgacgccagc accgccggcc gacatagaca ccgggatgtc
7200tccctgggcc actcggggaa tcgcggcgtt tttaggattt tggagtattt ttaccgtatg
7260tttcctatgc tacctgtgtt acctgcagtg ttgtggacgc tggtgtccca cgccgggaag
7320gggacgacga ggcggtgagg gctatcgacg cctaccgact tacgatagtt accccggtgt
7380tagaaagatg aagaggtgag aacacgcata aaataaaaaa atgagatatt aaaaaatgta
7440gtgtgtgaag tgtgaatagt atgattaaaa tatgcggatt gaatgggcgt gtttgttatt
7500cggatacttt gtgtcatccg ttgggagcga acggtcatta tcctatcgtt accacctgga
7560atctaattca tctaccaacg tggtttgcaa cggaaacatt tccgtgtttg taaacggcac
7620cctgggtgtt cggtatgacg ttacaatagg aatcggtagt ccatatccac tagtaggaca
7680cctcacaatc ataagtcttg aatcttggtt taaaccttgg attttaaaca caacttacaa
7740taaatatcca ttaaatacaa ctgaaacgtt ttataatgta gacgcggaaa atttacgtcg
7800cgtatcccaa tatttctaca aactagggtg ggtaaaaacg agtttacaag aaaatcacac
7860ctgtaacctc acaaacaata tacctaccta tgaatatcag gtaaacgtaa acaacacgga
7920ttacctaaca ctaatatcct cgggatggca agaccatcta aactacacca ccataaatag
7980tacacacttt aacctcacaa aatcgaacat aaccagcatt caaaaatatc tcaacactac
8040ctgcatagaa agactccgta actacacctt ggagcccgta tacaccacaa ctatgcctca
8100aaacgtaaca acacctcaac acataacaac cactctgtac acaacacctc caaatgcaat
8160aacaattcaa gatacaactc aaagccatac tgtacagacg ccgtctttta acgacacaca
8220taacgtgacg gaacacacgt taaacataag ctacgtttta tcacaaaaaa cgaataacac
8280aacatcaccg tgggtatatg ccatacctat gggcgccaca gccacaatag gcgccagttt
8340atatatcggg aaacacttta cgccggttag gtccgtatac gaagtatggc gcggtcagta
8400aagatgattc tgattcaaca catatacccc ccacgatcct cgaacacctt acagcatatg
8460agcaaaaaac aagaaagtat aaccacaatc acatttgggc gaataacacg ctgtcatcca
8520ctaacgtcta ttaatctaat gtttaacggg agctgtactg tcgccgttaa aatgtccatg
8580ggagtcaatg tacctgggta accgctgtca gccttggtga caggtgtaat cacagctgcc
8640acataactca cgaagcctcc aatcacagca gcacacacaa tcctaacgcc attggcgtgt
8700ataaaagttc ggaaaactcg acggttgtac ggcacgacaa atcgatgtag tggtatgtgt
8760ttccagcggg gaccgtgtgc ggtctcttag gttcgctata ctgtggctgg aaactggtta
8820cctgtgaaga tggctgacta tcctgttctg tcctggaaaa actttcagcg tcgtaggtgg
8880actttgcagt atgcggatta gtgaagttat gtcatttatt tacgtttacg atctcgtatt
8940acaaaccgcg gagaggatga taccgttcgg ccccatgagt tatttttatt cttccggtag
9000gaggcatgaa gcctctggtg atgctcatct gcttcggtgt gtttttacta cagcttgggg
9060gaagcaaaat gtgtaagccc gatgaggtga agctgggtaa ccaatgctgc ccgccatgcg
9120gatcaggaca aaaagttaca aaagtgtgta cagagaatag tggcataacg tgtacactgt
9180gcccaaacgg cacttatctc acagggcttt acaactgtac taattgtact caatgtaacg
9240acactcagat cacggttcgt aactgcactt ccactaataa caccatatgc gcatctaaga
9300atcatacatt gttttccact ccaggtgtcc aacatcacaa gcaacgacag caaaatcata
9360ccgcacatgt aaccgtcaaa caagggaaaa gtggtcgtca tactctagcc tggttgtccc
9420tcttcatctt tctcgtgggt atcatacttt taattctcta tcttatagcc gcctatcgga
9480gtgagagatg ccaacagtgt tgctcaatcg gcaaaatttt ctaccgcacc ctgtaagctt
9540cctgttgttg tttttacatc acggtacgat gaagtcacac agataattac agatgagctg
9600ttcatatttt ttattatttt ttccaattcc tgcactaaaa aaagaagcac tttacggaac
9660cgtgtctgaa tatctgtggg gaatttaggt actttttgcc gacgtcagga aaaataagct
9720gtcgcctaca taagagcccg gttctatcgt gctgtcactc tttcttgttg ccttcgatgt
9780acggcgtcct ggctcattac tactccttca tcagtagccc cagcgttatg gttaatttta
9840agcatcataa cgctgtacag ctgttgtgtg cacggacccg agacggcact gccggatggg
9900aacgtttaac ccatcatgcg tcgtatcacg cgaattatgg ggcatacgcc gtgttgatgg
9960ctacatcgca aagaaagtcc ctagtgttac atcgatatag tgccgtgaca gccgtggccc
10020tgcagctcat gcctgttgag atgctgcgca agctagacca gtcggactgg gtgcggggtg
10080cctggatcgt gtcagagact tttccaacta gcgaccccaa aggattttgg agcgacgatg
10140actcctcgat gggtggaagt gaagattgat gatgagaacc tgacaagaaa gacgatagag
10200aaattcagag ctgtcattgt agaattagtc tagattcctg ataataaacg gtatcgattt
10260tgaaacctaa ttgacgtgtg atcgattttt aaacctgtgt gttgtgtgat tgattggtac
10320gtggggggat ccgatttcaa agggaggtag ttatcgggaa ttgatgtgtc atggacgcag
10380ttttgagtga ttttccggga ataccggata ttacgaatta ctgtaagtga cgtcagaaat
10440taaattataa tgcgtttaat ttttggttta ttgatcattt ttattgttac agatacatgt
10500aacggcggtt ttggcactga aggtaatggt cgttgtgcat gcatagggta tcatcgactt
10560ttaggacaat tgcctcgtgg aactttctgg ttaggacatt taccaccagg ctcacattgc
10620ccaaagggac aagtcatgat aaagataggc caaggaccga tcgtctgttt atccgattat
10680catcctttat ctaagtggat gtatggaaat cataaatctg gttcggaaac atggcttcag
10740ataaaaatgg aaggtccaag aaatgctaca gtagtacaaa gatcgaatac tcgtccataa
10800agataacgaa tgttcataag aattgtactt ttatatgtat gtaagtttat ggatctttat
10860gtttgtcatc atatacatta gtagtaacat actcaacaca ctatgcgtgt acaatttgtt
10920ttatagatcc gtagtgtaca ataaatatta cgataaattt ttaacgtcgg atacatttac
10980gatactaaac gtactgtatt gcattttttg cacgatgttg acatcacatt gctgggctac
11040aagatggcat aacaaattat tggtacgata cctgtcattg actatatata tgttactgac
11100cgtatgtccc ctagccgtcc atcttttaga attggaagat tacgacagac gctgtcgttg
11160taacaatcaa attctgttga atactctgcc aatcggaact gaattgctta agccaatcgc
11220ggcgagcgaa agctgcaatc gtcaggaagt gctggctatt ttaaaggaca agggcaccaa
11280gtgtctcaat cctaacgcgc aagccgtgcg tcgtcacatc aaccggctat tttttcggtt
11340aatattagac gaggaacaac gcatttacga cgtagtgtct accaatattg agttcggtgc
11400ctggccagtc cctacggcct acaaagcctt tctctggaaa tacgccaaga aactgaacta
11460ccaccacttc agattgcgct ggtgatcatg tccctatttt accgtgcggt agccctgggc
11520acactgagcg ctctggtgtg gtacagcact agtatcctgg cagaaattaa cgaagaatcc
11580tgctcctcat cttctgtgga ccacgaagac tgcgaggaac cggacgagat cgttcgcgaa
11640gagcaagact atcgggctct gctggccttt tccctagtga tttgcggtac gctcctcgtc
11700acttgtgtga tctgagacgt catgctggta gcgtttatga gtcgggcggt ggccgacacg
11760ccgcatttcc taacccgcgc agcatgttgc gcttgctgtt cacgctcgtc ctgctggccc
11820tccacgggca gtctgtcggc gctagccgcg actatgtgca tgttcggcta ctgagctacc
11880gaggcgaccc cctggtcttc aagcacactt tctcgggtgt gcgtcgaccc ttcaccgagc
11940taggctgggc tgcgtgtcgc gactgggaca gtatgcattg cacacccttc tggtctaccg
12000atctggagca gatgaccgac tcggtgcggc gttacagcac ggtgagcccc ggtaaggaag
12060tgacgcttca gcttcacggg aaccaaaccg tacagccgtc gtttctaagc tttacgtgcc
12120gcctgcagct agaacccgtg gtggaaaatg ttggcctcta cgtggcctac gtggtcaacg
12180acggtgaacg cccacagcag ttttttacac cgcaggtaga cgtggtacgc tttgctctat
12240atctagaaac gctctcccgg atcgtggaac cgttagaatc aggtcgcctg gcagtggaat
12300ttgatacgcc tgacctagct ctggcgcccg atttagtaag cagcctcttc gtggccggac
12360acggcgagac cgacttttac atgaactgga cgctgcgtcg cagtcagacc cactacctgg
12420aggagatggc cttacaggtg gagattctaa agccacgcgg cgtacgtcac cgcgctatta
12480tccaccatcc gaagctacag ccgggcgttg gcctgtggat agatttctgc gtgtaccgct
12540acaacgcgcg cctgacccgc ggctacgtac gatacaccct gtcaccgaaa gcgcgcttgc
12600ccgcaaaagc agagggttgg ctggtgtcac tagacagatt catcgtgcag tacctcaaca
12660cattgctgat tacaatgatg gcggcgatat gggctcgcgt tttgataacc tacctggtgt
12720cgcggcgtcg gtagaggctt gcggaaacca cgtcctcgtc acacgtcgtt cgcggacata
12780gcaagaaatc cacgtcgcca cgtctcgaga atgccggccc cgcggggtct ccttcgcgca
12840acattcctgg ccctggtcgc gttcgggttg ctgctttaca tggacttcag cgacgctaca
12900aatatgacca gcagcacaaa cgtccctact agcaccagca gcagaaatac cgtcgagagc
12960accacgagta gcgaacctac aaccgaaacc aacatgacca ccgcccgcga atcttccgtt
13020cacgacgcgc gcaatgatga aatcatgaaa gtgctggcta tcctcttcta catcgtgaca
13080ggcacctcca ttttcagctt catagcggta ctgatcgcgg tagtttactc ctcgtgttgc
13140aagcacccgg gccgctttcg tttcgccgac gaagaggccg tcaacctgtt ggacgacacg
13200gacgacagtg gcggtagcag cccgtttggc agcggttccc gacgaggttc tcagatcccc
13260gccggatttt gttcctcgag cccttatcag cggttggaaa ctcgggactg ggacgaggag
13320gaggaggcgt ccgcggcccg cgagcgcatg aaacatgatc ctgagaacgt catctatttc
13380agaaaggatg gcaacttgga cacgtcgttc gtgaatccca attatgggag aggctcacct
13440ttgaccatcg aatctcacct ctcggacaat gaggaggacc ccatcaggta ctacgtttcg
13500gtgtacgatg aactgaccgc ctcggaaatg gaagaacctt cgaacagcac cagctggcag
13560attcccaaac taatgaaagt tgccatgcaa cccgtctcgc tcagagatcc cgagtacgac
13620taggcttttt tttttgtctt tcagttccaa ctctttcccc gccccatcac ctcgcctata
13680ctatgtgtat gatgtctcat aataaagctt tctttctcag tctgcaacat gcggctgtgt
13740cgggtgtggc tgtctgtttg tctgtgcgcc gtggtgctgg gtcagtgcca gcgggaaacc
13800gcggaaaaaa acgattatta ccgagtaccg cattactggg acgcgtgctc tcgcgcgctg
13860cccgaccaaa cccgttacaa gtatgtggaa cagctcgtgg acctcacgtt gaactaccac
13920tacgatgcga gccacggctt ggacaacttt gacgtgctca agaggtgagg atacgcgcta
13980aaggtgcatg acaacgggaa ggtaagggcg aacgggtaac gggtaagtaa ccgcatgggg
14040tatgaaatga cgtttggaac ctgtgcttgc agaatcaacg tgaccgaggt gtcgttgctc
14100atcagcgact ttagacgtca gaaccgtcgc ggcggcacca acaaaaggac cacgttcaac
14160gccgccggtt cgctggcgcc gcacgcccgg agcctcgagt tcagcgtgcg gctctttgcc
14220aactagcctg cgtcacggga aataatatgc tgcggcttct gcttcgtcac cactttcact
14280gcctgcttct gtgcgcggtt tgggcaacgc cctgtctggc gtctccgtgg tcgacgctaa
14340cggcaaacca gaatccgtcc ccgccatggt ctaaactgac gtattccaaa ccgcatgacg
14400cggcgacgtt ttactgtcct tttttctatc cctcgccccc acggtccccc ttgcaattct
14460cggggttcca gcaggtatca acgggtcccg agtgtcgcaa cgagaccctg tatctgctgt
14520acaaccggga aggccagacc ttggtagaga gaagctccac ctgggtgaaa aaggtgatct
14580ggtacctgag cggtcgcaac cagaccatcc ttcaacggat gccccgaacg gcttcgaaac
14640cgagcgacgg aaacgtgcag atcagcgtgg aagacgccaa gatttttgga gcgcacatgg
14700tgcccaagca gaccaagctg ctacgcttcg tcgtcaacga tggcacacgt tatcagatgt
14760gtgtgatgaa gctggagagc tgagctcacg tcttccggga ctacagcgtg tcttttcagg
14820tgcgattgac gttcaccgag gccaataacc agacttacac cttctgcacc catcccaatc
14880tcatcgtttg agcccgtcgc gcgcgcaggg aattttgaaa accgcgcgtc atgagtccca
14940aagacctgac gccgttcttg acggcgttgt ggctgctatt gggtcacagc cgcgtgccgc
15000gggtgcgcgc agaagaatgt tgcgaattca taaacgtcaa ccacccgccg gaacgctgtt
15060acgatttcaa aatgtgcaac cgcttcaccg tcgcgtacgt attttcatga ttgtctgcgt
15120tctgtggtgc gtctggatct gtctctcgac gtttctgata gccatgttcc atcgacgatc
15180ctcgggaatg ccagagtaga ttttcatgaa tccacaggct gcggtgtccg gacggcgaag
15240tctgctacag tcccgagaaa acggctgaga ttcgcgggat cgtcaccacc atgacccatt
15300cattgacgcg ccaggtcgta cacaacaaac tgacgagctg caactacaat ccgtaagtct
15360cttcctcgag ggccttacag cttatgggaa agtaagacag agagggacaa aacatcatta
15420aaaaaaaaaa gtctaatttc acgttttgta cccccccttc ccctccgtgt tgtaggttat
15480acctcgaagc tgacgggcga atacgctgcg gcaaagtgaa cgacaaggcg cagtacctgc
15540tgggcgccgc tggcagcgtt ccctatcgat ggatcaatct ggaatacgac aagataaccc
15600ggatcgtggg cctggatcag tacctggaga gcgttaagaa acacaaacgg ctggatgtgt
15660gccgcgctaa aatgggctat atgctgcagt gaataataaa atgtgtgttt gtccgaaata
15720cgcgtttcga gatttctgtc gccgactaaa ttcatgtcgc gcgatagtgg tgtttatcgc
15780cgatagagat ggcgatattg gaagaatcga tatttgaaaa tatggcatat tgaaaatgtc
15840gccgatgtga gtttctgtgt aactgatatc gccattttta aaaaagtgat ttttgggcat
15900atgcgatatc tggcgataac gcttatatcg tttacggggg atggcgatag acgactttgg
15960cgacttgggc gattctgtgt gtcgcaaata tcgcagtttc gatataggtg acagacgata
16020tgaggccata tcgccgatag aggcgacatc aagttggcac atggccaatg catatcgata
16080tatacattga atcaatattg gccattagcc acattagtca ttggttatat agtataaatc
16140aatattggct aatggccatt gcatacgttg tatctatatc ataatatgta catttatatt
16200ggctcatatc caatataacc gccatgttga cattgattat tgattagtta ttaatagtaa
16260tcaattacgg ggtcattagt tcatagccca tatatggagt tccgcgttac ataacttacg
16320gtaaatggcc cgcctggctg accgcccaac gacccccgcc cattgacgtc aataatgacg
16380tgagttccca tagtaacacc aatagggact ttccattgac gtcaatggga ggagtattta
16440cggtaaactg cccacttggc agtacatcaa gtgtatcata tgccaagtac gccccctatt
16500gacgtcaatg acggtaaatg gcccgcctgg cattatgccc agtacatgac cttacgggac
16560tttcctactt
1657036141DNAHuman cytomegalovirus 3tttaaacctg tgtgttgtgt gattgattgg
tacgtggggg gatccgattt caaagggagg 60tagttatcgg gagttgatgt gtcatggacg
tagttttgag tgattttccg ggaataccgg 120atattacgaa ttactaatag tgacgtagat
aataaaatta taatgcgatt tatttttagt 180ctgtttggtc ttttgatcgc gttgtgctat
aaggtggaaa gtgtggaact acgttgtcgg 240tgtagcaatg gttcaaatca tcccgtattc
ggcgtttttt gggtcggcta taaacctcca 300gatcctacat gcgacaaaac gcaacacttt
ttattacctc cccgacaaac acctgtatgt 360ttgtctcctg atcattatct atcgaaatgg
gttgatggca aacgaagtaa ctggtggcat 420aaagtgttta taaagaaaaa ctctgataat
ggaccacata tagaagacaa aagtgacacc 480aatagacacc cgccttggcg actataattt
tttataaatt gtaaaacgag ttggcaatat 540cacgtatata gcgaaaaagg taatacaatg
tgttttcgac atggttttga catggttaca 600ccatccgatt ccaaattcgc acatcaaagt
cttatcggta cgatacctgt atttgaccgc 660atatgtgtta ttttccacgt gtcccctatt
cgtctatctc ttagaattgg aagattacga 720caagcgctgt cgttgcaaca accaaattct
gttgaatacc ctgccagtcg gaactcaact 780gcttaagcca atcgcagcga gcgaaagctg
caatcgtcag gaagtgctgg ctattttaaa 840ggacaagggc accaagtgtc tcaatcctaa
cgcgcaagct gtgcgtcgtc acatcaaccg 900gctatttttt cggttaatct tagacgaaga
acaacgcatt tacgacgtag tgtctaccaa 960tattgagttt ggtgcctggc cagcccctac
ggcctacaaa gcctttctct ggaaatacgc 1020caagaaattg aactaccacc acttcagact
gcgctggtga tcatgtccct attttaccgt 1080gcggtagctc tgggcacact aagcgctctg
gtgtggtaca gcactagtat cctcgcagag 1140attaacgaaa attcctgctc ctcatcttct
gtggaccacg aagagtgtga ggaaccggac 1200gagatcgttc gcgaagagca agactatcgg
gctctgctgg ccttttccct agtgatttgc 1260ggtacgctcc tcgtcacttg tgtgatctga
gacgtcatgc tggtagtgtt tatgagtcgg 1320gcggtggccg gcacgccgca tttcctaacc
cgcgcagcat gttgcgcttg ctgttcacgc 1380tcgtcctgct ggccctccac gggccgtctg
tcaatgctag ccgcgactat gtgcatgttc 1440ggctattgag ctaccgaggc gaccccctgg
tcttcaagca cactttttcg ggtgtgcgtc 1500gacccttcac cgagctaggc tgggctgcgt
gtcgcgactg ggacagtatg cattgcacgc 1560ccttctggtc taccgatccg gagcagatga
ccgactcggt gcggcgttac agcacagtga 1620gccccggcaa ggaagtgacg cttcagcttc
acgggaacca aaccgtacag ccgtcgtttc 1680taagctttac gtgccgcctg cagctagaac
ccgtggtgga aaatgttggc ctctacgtgg 1740cctacgtggt caacgacggt gaacgcccac
agcagttttt tacaccgcag gtagacgtgg 1800tacgctttgc tctatatcta gagacgctct
cccggatcgt ggaaccgtta gaatcaggtc 1860gcctggcagt ggaatttgat acgcctgacc
tagctctggc gcccgattta gtaagcagcc 1920tcttcgtggc cggacacggc gagaccgact
tttacatgaa ctggacgctg cgtcgcagtc 1980agacccacta cctggaggag atggccttac
aggtggagat tctaaagccc cgcggcgtac 2040gtcaccgcgc tattatccac catccgaagc
tacagccggg cgttggcctg tggatagatt 2100tctgcgtgta ccgctacaac gcgcgcctga
cccgcggcta cgtacgatac accctgtcac 2160cgaaagcgcg cttgcccgca aaagcagagg
gttggctggt gtcactagac agattcatcg 2220tgcagtacct caacacattg ctgattacaa
tgatggcggc gatatgggct cgcgttttga 2280taacctacct ggtgtcgcgg cgtcggtaga
ggcttgcgga aaccacgtcc tcgtcacacg 2340tcgttcgcgg acatagcaag aaatccacgt
cgccacgtct cgagaatgcc ggccccgcgg 2400ggtccccttc gcgcaacatt cctggccctg
gtcgcgttcg ggttgctgct tcagatagac 2460ctcagcgacg ctacgaatgt gaccagcagc
acaaaagtcc ctactagcac cagcagcaga 2520aatagcgtcg acaatgccac gagtagcgga
cccacgaccg ggatcaacat gaccaccacc 2580cacgagtctt ccgttcacag cgtgcgcaat
gacgaaatca tgaaagtgct ggctatcctc 2640ttctacatcg tgacaggcac ctccattttc
agcttcatag cggtactgat cgcggtagtt 2700tactcctcgt gttgcaagca cccgggccgc
tttcgtttcg ccgacgaaga agccgtcaac 2760ctgttggacg acacggacga cagtggcggt
ggcagcccgt ttggcagcgg ttcccgacga 2820ggttctcaga tccccgccgg attttgttcc
tcgagccctt atcagcggtt ggaaactcgg 2880gactgggacg aggaggagga ggcgtccgcg
gcccgcgagc gcatgaaaca tgatcctgag 2940aacgtcatct atttcagaaa ggatggcaac
ttggacacgt cgttcgtgaa tcccaattat 3000gggagaggct cgcctttgac catcgaatct
cacctctcgg acaatgagga agaccccatc 3060aggtactacg tctcggtgta cgatgaactg
accgcctcgg aaatggaaga accttcgaac 3120agcaccagct ggcagattcc caaactaatg
aaagttgcca tgcaacccgt ctcgctcaga 3180gatcccgagt acgactaggc tttttttttt
ttatctttcg gttccaactc tttccccgcc 3240ccatcacctc gcctatacta tgtgtatgat
gtctcataat aaagctttct ttctcagtct 3300gcaacatgcg gctgtgtcgg gtgtggctgt
ctgtttgtct gtgcgccgtg gtgctgggtc 3360agtgccagcg ggagaccgca gaaaaaaacg
attattaccg agtaccgcat tactgggacg 3420cgtgctctcg cgcgctgccc gaccaaaccc
gttacaagta tgtggaacag ctcgtggacc 3480tcacgttgaa ctaccactac gatgcgagcc
acggcttgga caactttgac gtgctcaaga 3540ggtgaggata cgcgctaaag gtgtatgaca
acgggaaggt aagggcgaac gggtaacggg 3600caggtaaccg catggggtgt gaaatgacgt
tcggaacctg tgcttgcaga atcaacgtga 3660ccgaggtgtc gttgctcatc agcgacttta
gacgtcagaa ccgtcgcggc ggcaccaaca 3720aaaggaccac gttcaacgcc gccggttcgc
tggcgccgca cgcccggagc ctcgagttca 3780gcgtgcggct ctttgccaac tagcctgcgt
cacgggaaat aatatgctac ggcttctgct 3840tcgtcaccac tttcactgcc tgcttctgtg
cgcggtttgg gcaacgccct gtctggcgtc 3900tccgtggtca acgctaacgg cgaaccagaa
tccgtccccg ctatggtcta aactgacgta 3960ttccaaaccg catgacgcgg cgacgtttta
ctgtcctttt atctatccct cgcccccacg 4020gtcccccttg caattctcgg ggttccagcg
ggtattaacg ggtcccgagt gtcgcaacga 4080gaccctgtat ctgctgtaca accgggaagg
ccagaccttg gtggagagaa gctccacctg 4140ggtgaaaaag gtgatctggt acctgagcgg
tcgcaaccag accatcctcc aacggatgcc 4200ccgaacggct tcaaaaccga gcgacggaaa
cgtgcagatc agcgtggaag acgccaagat 4260ttttggagcg cacatggtgc ccaagcagac
caagctgcta cgcttcgtcg tcaacgatgg 4320cacacgttat cagatgtgtg tgatgaagct
ggagagctgg gctcacgtct tccgggacta 4380cagcgtgtct tttcaggtgc gattgacgtt
caccgaggcc aataaccaga cttacacctt 4440ctgcacccat cccaatctca tcgtttgagc
ccgtcgcgcg cgcagggaat tttgaaaacc 4500gcgcgtcatg agtcccaaaa acctgacgcc
gttcttgacg gcgttgtggc tgttattgga 4560tcacagccgc gtgccgcggg tacgcgcaga
agaatgttgc gaattcataa acgtcaacca 4620cccgccggaa cgctgttacg atttcaaaat
gtgcaatcgc ttcaccgtcg cgtacgtatt 4680ttcatgattg tctgcgttct gtggtgcgtc
tggatctgtc tctcgacgtt tctgatagcc 4740atgttccatc gacgatcctc gggaatgcca
gagtagattt tcatgaatcc acaggctgcg 4800gtgtccggac ggcgaagtct gctacagtcc
cgagaaaaac ggctgagatt cgcgggatcg 4860tcaccaccat gacccattca ttgacacgcc
aggtcgtaca caacaaactg acgagctgca 4920actacaatcc gtaagtctct tcctcgaggg
ccttacagcc tatgggagag taagacagag 4980agggacaaaa catcattaaa aaaaaaagtc
taatttcacg ttttgtaccc cccttccgtg 5040ttgtaggtta tacctcgaag ctgacgggcg
aatacgctgc ggcaaagtga acgacaaggc 5100gcagtacctg ctgggcgccg ctggcagcgt
tccctatcga tggatcaacc tggaatacga 5160caagataacc cggatcgtgg gcctggatca
gtacctggag agcgttaaga aacacaaacg 5220gctggatgtg tgccgcgcta aaatgggcta
tatgctgcag tgaataataa aatgtgtgtt 5280tgtccgaaat acgcgttttg agatttctgt
cgccgactaa attcatgtcg cgcgatagtg 5340gtgtttatcg ccgatagaga tggcgatatt
ggaaaaatca atatttgaaa atatggcata 5400ttgaaaatgt cgccgatgtg agtttctgtg
taactgatat cgccattttt ccaaaagtga 5460tttttgggca tacgcgatat ctggcgatag
cgcttatatc gtttacgggg gatggcgata 5520gacgactttg gcgacttggg cgattcggtg
tgtcgcaaat atcgcagttt cgatataggt 5580gacagacgat atgaggccat atcgccgata
gaggcgacat cgagttggca catggccaat 5640ggatatcgat atatacattg catcaatatt
ggccattagc catattagtc attggttata 5700tagcgtaaat caatattggc taatggccat
tgcatacgtt gcatctatat cataatgtgt 5760acatttatat tggctcatgt ccaatatgac
cgccatgttg acattgatta ttgactagtt 5820attaatagta atcaattacg gggtcattag
ttcatagccc atatatggag ttccgcgtta 5880cataacttac ggtaaatggc ccgcctggct
gaccgcccaa cgacccccgc ccattgacgt 5940caataatgac gtgggttccc atagtaacgc
caatagggac tttccattga cgtcaatggg 6000aggagtattt acggtaaact gcccacttgg
cagtacatca agtgtatcat atgccaagta 6060cgccccctat tgacgtcaat gacggtaaat
ggcccgcctg gcattatgcc cagtacatga 6120ccttacggga ctttcctact t
614146138DNAHuman cytomegalovirus
4tttaaacctg tgtgttgtgt gattgattgg tacgtggggg gatccgattt caaagggagg
60tagttatcgg gagttgatgt gtcatggacg tagttttgag tgattttccg ggaataccgg
120atattacgaa ttactgatag tgacgtagat aataaaatta taatgcgatt tatttttagt
180ctgtttggtc ttttgatcgc gttgtgctat aaggtggaaa gtgtggaact acgttgtcgg
240tgtagcaatg gttcaaatca tcccgtattc ggcgtttttt gggtcggcta taaacctcca
300gatcctacat gcgacaaaac gcaacacttt ttattacctc cccgacaaac acctgtatgt
360ttgtctcctg atcattatct atcgaaatgg gttgatggca aacgaagtaa ctggtggcat
420aaagtgttta taaagaaaaa ctctgataat ggaccacata tagaagacaa aagtgacacc
480aatagacacc cgccttggcg actataattt tttataaatt gtaaaacgag ttggcaatat
540cacgtatata gcgaaaaagg taatacaatg tgttttcgac atggttttga catggttaca
600ccatccgatt ccaaattcgc acatcaaagt cttatcggta cgatacctgt atttgaccgc
660atatgtgtta ttttccacgt gtcccctatt cgtctatctc ttagaattgg aagattacga
720caagcgctgt cgttgcaaca accaaattct gttgaatacc ctgccagtcg gaactcaact
780gcttaagcca atcgcagcga gcgaaagctg caatcgtcag gaagtgctgg ctattttaaa
840ggacaagggc accaagtgtc tcaatcctaa cgcgcaagct gtgcgtcgtc acatcaaccg
900gctatttttt cggttaatct tagacgaaga acaacgcatt tacgacgtag tgtctaccaa
960tattgagttt ggtgcctggc cagcccctac ggcctacaaa gcctttctct ggaaatacgc
1020caagaaattg aactaccacc acttcagact gcgctggtga tcatgtccct attttaccgt
1080gcggtagctc tgggcacact aagcgctctg gtgtggtaca gcactagtat cctcgcagag
1140attaacgaaa attcctgctc ctcatcttct gtggaccacg aagagtgtga ggaaccggac
1200gagatcgttc gcgaagagca agactatcgg gctctgctgg ccttttccct agtgatttgc
1260ggtacgctcc tcgtcacttg tgtgatctga gacgtcatgc tggtagtgtt tatgagtcgg
1320gcggtggccg gcacgccgca tttcctaacc cgcgcagcat gttgcgcttg ctgttcacgc
1380tcgtcctgct ggccctccac gggccgtctg tcaatgctag ccgcgactat gtgcatgttc
1440ggctattgag ctaccgaggc gaccccctgg tcttcaagca cactttttcg ggtgtgcgtc
1500gacccttcac cgagctaggc tgggctgcgt gtcgcgactg ggacagtatg cattgcacgc
1560ccttctggtc taccgatccg gagcagatga ccgactcggt gcggcgttac agcacagtga
1620gccccggcaa ggaagtgacg cttcagcttc acgggaacca aaccgtacag ccgtcgtttc
1680taagctttac gtgccgcctg cagctagaac ccgtggtgga aaatgttggc ctctacgtgg
1740cctacgtggt caacgacggt gaacgcccac agcagttttt tacaccgcag gtagacgtgg
1800tacgctttgc tctatatcta gagacgctct cccggatcgt ggaaccgtta gaatcaggtc
1860gcctggcagt ggaatttgat acgcctgacc tagctctggc gcccgattta gtaagcagcc
1920tcttcgtggc cggacacggc gagaccgact tttacatgaa ctggacgctg cgtcgcagtc
1980agacccacta cctggaggag atggccttac aggtggagat tctaaagccc cgcggcgtac
2040gtcaccgcgc tattatccac catccgaagc tacagccggg cgttggcctg tggatagatt
2100tctgcgtgta ccgctacaac gcgcgcctga cccgcggcta cgtacgatac accctgtcac
2160cgaaagcgcg cttgcccgca aaagcagagg gttggctggt gtcactagac agattcatcg
2220tgcagtacct caacacattg ctgattacaa tgatggcggc gatatgggct cgcgttttga
2280taacctacct ggtgtcgcgg cgtcggtaga ggcttgcgga aaccacgtcc tcgtcacacg
2340tcgttcgcgg acatagcaag aaatccacgt cgccacgtct cgagaatgcc ggccccgcgg
2400ggtccccttc gcgcaacatt cctggccctg gtcgcgttcg ggttgctgct tcagatagac
2460ctcagcgacg ctacgaatgt gaccagcagc acaaaagtcc ctactagcac cagcagcaga
2520aatagcgtcg acaatgccac gagtagcgga cccacgaccg ggatcaacat gaccaccacc
2580cacgagtctt ccgttcacag cgtgcgcaat gacgaaatca tgaaagtgct ggctatcctc
2640ttctacatcg tgacaggcac ctccattttc agcttcatag cggtactgat cgcggtagtt
2700tactcctcgt gttgcaagca cccgggccgc tttcgtttcg ccgacgaaga agccgtcaac
2760ctgttggacg acacggacga cagtggcggt ggcagcccgt ttggcagcgg ttcccgacga
2820ggttctcaga tccccgccgg attttgttcc tcgagccctt atcagcggtt ggaaactcgg
2880gactgggacg aggaggagga ggcgtccgcg gcccgcgagc gcatgaaaca tgatcctgag
2940aacgtcatct atttcagaaa ggatggcaac ttggacacgt cgttcgtgaa tcccaattat
3000gggagaggct cgcctttgac catcgaatct cacctctcgg acaatgagga agaccccatc
3060aggtactacg tctcggtgta cgatgaactg accgcctcgg aaatggaaga accttcgaac
3120agcaccagct ggcagattcc caaactaatg aaagttgcca tgcaacccgt ctcgctcaga
3180gatcccgagt acgactaggc tttttttttt ttatctttcg gttccaactc tttccccgcc
3240ccatcacctc gcctatacta tgtgtatgat gtctcataat aaagctttct ttctcagtct
3300gcaacatgcg gctgtgtcgg gtgtggctgt ctgtttgtct gtgcgccgtg gtgctgggtc
3360agtgccagcg ggagaccgca gaaaaaaacg attattaccg agtaccgcat tactgggacg
3420cgtgctctcg cgcgctgccc gaccaaaccc gttacaagta tgtggaacag ctcgtggacc
3480tcacgttgaa ctaccactac gatgcgagcc acggcttgga caactttgac gtgctcaaga
3540ggtgaggata cgcgctaaag gtgtatgaca acgggaaggt aagggcgaac gggtaacggg
3600caggtaaccg catggggtgt gaaatgacgt tcggaacctg tgcttgcaga atcaacgtga
3660ccgaggtgtc gttgctcatc agcgacttta gacgtcagaa ccgtcgcggc ggcaccaaca
3720aaaggaccac gttcaacgcc gccggttcgc tggcgccgca cgcccggagc ctcgagttca
3780gcgtgcggct ctttgccaac tagcctgcgt cacgggaaat aatatgctac ggcttctgct
3840tcgtcaccac tttcactgcc tgcttctgtg cgcggtttgg gcaacgccct gtctggcgtc
3900tccgtggtca acgctaacgg cgaaccagaa tccgtccccg ctatggtcta aactgacgta
3960ttccaaaccg catgacgcgg cgacgtttta ctgtcctttt atctatccct cgcccccacg
4020gtcccccttg caattctcgg ggttccagcg ggtattaacg ggtcccgagt gtcgcaacga
4080gaccctgtat ctgctgtaca accgggaagg ccagaccttg gtggagagaa gctccacctg
4140ggtgaaaaag gtgatctggt acctgagcgg tcgcaaccag accatcctcc aacggatgcc
4200ccgaacggct tcaaaaccga gcgacggaaa cgtgcagatc agcgtggaag acgccaagat
4260ttttggagcg cacatggtgc ccaagcagac caagctgcta cgcttcgtcg tcaacgatgg
4320cacacgttat cagatgtgtg tgatgaagct ggagagctgg gctcacgtct tccgggacta
4380cagcgtgtct tttcaggtgc gattgacgtt caccgaggcc aataaccaga cttacacctt
4440ctgcacccat cccaatctca tcgtttgagc ccgtcgcgcg cgcagggaat tttgaaaacc
4500gcgcgtcatg agtcccaaaa acctgacgcc gttcttgacg gcgttgtggc tgttattgga
4560tcacagccgc gtgccgcggg tacgcgcaga agaatgttgc gaattcataa acgtcaacca
4620cccgccggaa cgctgttacg atttcaaaat gtgcaatcgc ttcaccgtcg cgtacgtatt
4680ttcatgattg tctgcgttct gtggtgcgtc tggatctgtc tctcgacgtt tctgatagcc
4740atgttccatc gacgatcctc gggaatgcca gagtagattt tcatgaatac acaggctgcg
4800gtgtccggac ggcgaagtct gctacagtcc cgagaaaacg gctgagattc gcgggatcgt
4860caccaccatg acccattcat tgacacgcca ggtcgtacac aacaaactga cgagctgcaa
4920ctacaatccg taagtctctt cctcgagggc cttacagcct atgggagagt aagacagaga
4980gggacaaaac atcattaaaa aaaaaagtct aatttcacgt tttgtacccc ccttccgtgt
5040tgtaggttat acctcgaagc tgacgggcga atacgctgcg gcaaagtgaa cgacaaggcg
5100cagtacctgc tgggcgccgc tggcagcgtt ccctatcgat ggatcaacct ggaatacgac
5160aagataaccc ggatcgtggg cctggatcag tacctggaga gcgttaagaa acacaaacgg
5220ctggatgtgt gccgcgctaa aatgggctat atgctgcagt gaataataaa atgtgtgttt
5280gtccgaaata cgcgttttga gatttctgtc gccgactaaa ttcatgtcgc gcgatagtgg
5340tgtttatcgc cgatagagat ggcgatattg gaaaaatcaa tatttgaaaa tatggcatat
5400tgaaaatgtc gccgatgtga gtttctgtgt aactgatatc gccatttttc caaaagtgat
5460ttttgggcat acgcgatatc tggcgatagc gcttatatcg tttacggggg atggcgatag
5520acgactttgg cgacttgggc gattcggtgt gtcgcaaata tcgcagtttc gatataggtg
5580acagacgata tgaggccata tcgccgatag aggcgacatc gagttggcac atggccaatg
5640gatatcgata tatacattgc atcaatattg gccattagcc atattagtca ttggttatat
5700agcgtaaatc aatattggct aatggccatt gcatacgttg catctatatc ataatgtgta
5760catttatatt ggctcatgtc caatatgacc gccatgttga cattgattat tgactagtta
5820ttaatagtaa tcaattacgg ggtcattagt tcatagccca tatatggagt tccgcgttac
5880ataacttacg gtaaatggcc cgcctggctg accgcccaac gacccccgcc cattgacgtc
5940aataatgacg tgggttccca tagtaacgcc aatagggact ttccattgac gtcaatggga
6000ggagtattta cggtaaactg cccacttggc agtacatcaa gtgtatcata tgccaagtac
6060gccccctatt gacgtcaatg acggtaaatg gcccgcctgg cattatgccc agtacatgac
6120cttacgggac tttcctac
613851245DNAHuman cytomegalovirus 5cggcacacat ccagccgttt gtgtttctta
acgctctcca ggtactgatc caggcccacg 60atccgggtta tcttgtcgta ttccaggttg
atccatcgat agggaacgct gccagcggcg 120cccagcaggt actgcgcctt gtcgttcact
ttgccgcagc gtattcgccc gtcagcttcg 180aggtataacg gattgtagtt gcagctcgtc
agtttgttgt gtacgacctg gggtgtcaat 240gaatgggtca tggtggtgac gatcccgcga
atctcagccg ttttctcggg actgtagcag 300acttcgccgt ccggacaccg cagcctgtgg
attcatgaaa atctactctg gcattcccga 360ggatcgtcga tggaacatgg ctatcagaaa
cgtcgagaga cagatccaga cgcaccacag 420aacgcagaca atcatgaaaa tacgtacgcg
acggtgaagc gattgcacat tttgaaatcg 480taacagcgtt ccggcgggtg gttgacgttt
atgaattcgc aacattcttc tgcgcgtacc 540cgcggcacgc ggctgtgacc caatagcagc
cacaacgccg tcaagaacgg cgtcaggttt 600ttgggactca tgacgcgcgg ttttcaaaat
tccctgcgcg cgcgacgggc tcaaacgatg 660agattgggat gggtgcagaa ggtgtaagtc
tggttattgg cctcggtgaa cgtcaatcgc 720acctgaaaag acacgctgta gtcccggaag
acgtgggccc agctctccag tttcatcaca 780cacatctgat aacgtgtgcc gtcgttgacg
acgaaacgta gcagcttggt ctgcttgggc 840accatgtgcg ctccaaaaat cttggcgtct
tccacgctga tctgcacgtt tccgtcgctc 900ggtttcgaag ccgttcgggg catccgttgg
aggatggtct gattgcgacc gctcagatac 960cagatcacct ttttcaccca ggtggagctt
ctctccacca aggtctggcc ttcccggttg 1020tacagcagat acagggtctc gttgcgacac
tcgggacccg ttgatacccg ctggaacccc 1080gggaattgcg agggggaccg tgggggcgag
ggatagagaa aaggacagta aaacgtcgcc 1140gcgtcatgcg gtttgggata cgtcagttta
gaccatggcg gggacggatt ctccccgcgt 1200actctgcgtt gttaccactg cttgccctat
agtgagtcgt attag 124561814DNAHuman cytomegalovirus
6tgtgtcgggt gtggctgtct gtttgtctgt gcgccgtggt gctgggtcag tgccagcggg
60agaccgcaga aaaaaacgat tattaccgag taccgcatta ctgggacgcg tgctctcgcg
120cgctgcctga ccaaacccgt tacaagtatg tggaacagct cgtggacctc acgttgaact
180accactacga tgcgagccac ggcttggaca actttgacgt gctcaagaga atcaacgtga
240ccgaggtgtc gttgctcatc agcgacttta gacgtcagaa ccgtcgcggc ggcaccaaca
300aaaggaccac gttcaacgcc gccggttcgc tggcgcctca cgcccggagc ctcgagttca
360gcgtgcggct ctttgccaac tagcctgcgt cacgggaaat aatatgctac ggcttctgct
420tcgtcaccac tttcactgcc tgcttctgtg cgcggtttgg gcaacgccct gtctggcgtc
480tccgtggttc acgctaacgg cgaaccagaa tccgtccccg ccatggtcta aactgacgta
540tcccaaaccg catgacgcgg cgacgtttta ctgtcctttt ctctatccct cgcccccacg
600gtccccctcg caattcccgg ggttccagcg ggtatcaacg ggtcccgagt gtcgcaacga
660gaccctgtat ctgctgtaca accgggaagg ccagaccttg gtggagagaa gctccacctg
720ggtgaaaaag gtgatctggt atctgagcgg tcgcaatcag accatcctcc aacggatgcc
780ccgaacggct tcgaaaccga gcgacggaaa cgtgcagatc agcgtggaag acgccaagat
840ttttggagcg cacatggtgc ccaagcagac caagctgcta cgtttcgtcg tcaacgatgg
900cacacgttat cagatgtgtg tgatgaaact ggagagctgg gcccacgtct tccgggacta
960cagcgtgtct tttcaggtgc gattgacgtt caccgaggcc aataaccaga cttacacctt
1020ctgcacccat cccaatctca tcgtttgagc ccgtcgcgcg cgcagggaat tttgaaaacc
1080gcgcgtcatg agtcccaaaa acctgacgcc gttcttgacg gcgttgtggc tgctattggg
1140tcacagccgc gtgccgcggg tacgcgcaga agaatgttgc gaattcataa acgtcaacca
1200cccgccggaa cgctgttacg atttcaaaat gtgcaatcgc ttcaccgtcg cgtacgtatt
1260ttcatgattg tctgcgttct gtggtgcgtc tggatctgtc tctcgacgtt tctgatagcc
1320atgttccatc gacgatcctc gggaatgcca gagtagattt tcatgaatcc acaggctgcg
1380gtgtccggac ggcgaagtct gctacagtcc cgagaaaacg gctgagattc gcgggatcgt
1440caccaccatg acccattcat tgacacgcca ggtcgtacac aacaaactga cgagctgcaa
1500ctacaatccg ttatacctcg aagctgacgg gcgaatacgc tgcggcaaag tgaacgacaa
1560ggcgcagtac ctgctgggcg ccgctggcag cgttccctat cgatggatca acctggaata
1620cgacaagata acccggatcg tgggcctgga tcagtacctg gagagcgtta agaaacacaa
1680acggctggat gtgtgccgcg ctaaaatggg ctatatgctg cagtgaataa taaaatgtgt
1740gtttgtcaaa aaaaaaaaaa aaaaaaagta ctctgcgttg ttaccactgc ttgccctata
1800gtgagtcgta ttag
181471951DNAHuman cytomegalovirus 7gaattcggct ttgtgtcggg taaggctgtc
tgtttgtctg tgcgccgtgg tgctgggtca 60gtgccagcgg gagaccgcag aaaaaaacga
ttattaccga gtaccgcatt actgggacgc 120gtgctctcgc gcgctgcctg accaaacccg
ttacaagtat gtggaacagc tcgtggacct 180cacgttgaac taccactacg atgcgagcca
cggcttggac aactttgacg tgctcaagag 240gtgagggtac gcgctaaagg tgtatgacaa
cgggaaggta agggcgaacg ggtaacgggt 300aggtaaccgc atggggtgtg aaatgacgtt
cggaacctgt gcttgcagaa tcaacgtgac 360cgaggtgtcg ttgctcatca gcgactttag
acgtcagaac cgtcgcggcg gcaccaacaa 420aaggaccacg ttcaacgccg ccggttcgct
ggcgcctcac gcccggagcc tcgagttcag 480cgtgcggctc tttgccaact agcctgcgtc
acgggaaata atatgctacg gcttctgctt 540cgtcacactt tcactgcctg cttctgtgcg
cggtttgggc aacgccctgt ctggcgtctc 600cgtggttcac gctaacggcg aaccagaatc
cgtccccgcc atggtctaaa ctgacgtatc 660ccaaaccgca tgacgcggcg acgttttact
gtccttttct ctatccctcg cccccacggt 720ccccctcgca attcccgggg ttccagcggg
tatcaacggg tcccgagtgt cgcaacgaga 780ccctgtatct gctgtacaac cgggaaggcc
agaccttggt ggagagaagc tccacctggg 840tgaaaaaggc gatctggtat ctgagcggtc
gcaatcagac catcctccaa cggatgcccc 900gaacggcttc gaaaccgagc gacggaaacg
tgcagatcag cgtggaagac gccaagattt 960ttggagcgca catggtgccc aagcagacca
agctgctacg tttcgtcgtc aacgatggca 1020cacgttatca gatgtgtgtg atgaaactgg
agagctgggc ccacgtcttc cgggactaca 1080gcgtgtcttt tcaggtgcga ttgacgttca
ccgaggccaa taaccagact tacaccttct 1140gcacccatcc caatctcatt gtttgagccc
gtcgcgcgcg cagggaattt tgaaaaccgc 1200gcgtcatgag tcccaaaaac ctgacgccgt
tcttgacggc gttgtggctg ctattgggtc 1260acagccgcgt gccgcgggta cgcgcagaag
aatgttgcga attcataaac gtcaaccacc 1320cgccggaacg ctgttacgat ttcaaaatgt
gcaatcgctt caccgtcgcg tacgtatttt 1380catgattgtc tgcgttctgt ggtgcgtctg
gatctgtctc tcgacgtttc tgatagccat 1440gttccatcga cgatcctcgg gaatgccaga
gtagattttc atgaatccac aggctgcggt 1500gtccggacgg cgaagtctgc tacagtcccg
agaaaacggc tgagattcgc gggatcgtca 1560ccaccatgac ccattcattg acacgccagg
tcgtacacaa caaactgacg agctgcaact 1620acaatccgtt atacctcgaa gctgacgggc
gaatacgctg cggcaaagtg aacgacaagg 1680cgcagtacct gctgggcgcc gctggcagcg
ttccctatcg atggatcaac ctggaatacg 1740acaagataac ccggatcgtg ggcctggatc
agtacctgga gagcgttaag aaacacaaac 1800ggctggatgt gtgccgcgct aaaatgggct
atatgctgca gtgaataata aaatgtgtgt 1860ttgtccggaa aaaaaaaaaa aaaagaaaaa
aaagtactct gcgttgttac cactgcttgc 1920cctatagtga gtcgtattag aagccgaatt c
19518651DNAHuman cytomegalovirus
8gaattcggct tctaatacga ctcactatag ggcaagcagt ggtaacaacg cagagtacgc
60gggggtcctt ttctctatcc ctcgccccca cggtccccct cgcaattccc ggggttccag
120cgggtatcaa cgggtcccga gtgtcgcaac gagaccctgt atctgctgta caaccgggaa
180ggccagacct tggtggagag aagctccacc tgggtgaaaa aggtgatctg gtatctgagc
240ggtcgcaatc agaccatcct ccaacggatg ccccgaacgg cttcgaaacc gagcgacgga
300aacgtgcaga tcagcgtgga agacgccaag atttttggag cgcacatggt gcccaagcag
360accaagctgc tacgtttcgt cgtcaacgat ggcacacgtt atcagatgtg tgtgatgaaa
420ctggagagct gggcccacgt cttccgggac tacagcgtgt cttttcaggt gcgattgacg
480ttcaccgagg ccaataacca gacttacacc ttctgcaccc atcccaatct catcgtttga
540gcccgtcgcg cgcgcaggga attttgaaaa ccgcgcgtca tgagtcccaa aaacctgacg
600ccgttcttga cggcgttgtg gctgctattg ggtcacagcc gcgtgccgcg g
6519581DNAHuman cytomegalovirus 9gaattcggct tcggcacaca tccagccgtt
tgtgtttctt aacgctctcc aggtactgat 60ccaggcccac gatccgggtt atcttgtcgt
attccaggtt gatccatcga tagggaacgc 120tgccagcggc gcccagcagg tactgcgcct
tgtcgttcac tttgccgcag cgtattcgcc 180cgtcagcttc gaggtataac ggattgtagt
tgcagctcgt cagtttgttg tgtacgacct 240ggcgtgtcaa tgaatgggtc atggtggtga
cgatcccgcg aatctcagcc gttttctcgg 300gactgtagca gacttcgccg tccggacacc
gcagcctgtg gattcatgaa aatctactct 360ggcattcccg gggatcgtcg atggaacatg
gctatcagaa acgtcgagag acagatccag 420acgcaccaca gaacgcagac gatcatgaaa
atacgtacgc gacggtgaag cgattgcaca 480ttttgaaatc gtaacagcgt tccggcgggt
gtttgacgtt tatgaattcg caacattctt 540ctgcgcgtac ccgcggcacg cggctgtgac
ccaatagcag c 58110547DNAHuman cytomegalovirus
10gaattcggct tcggcacaca tccagccgtt tgtgtttctt aacgctctcc aggtactgat
60ccaggcccac gatccgggtt atcttgtcgt attccaggtt gatccatcga tagggaacgc
120tgccagcggc gcccagcagg tactgcgcct tgtcgttcac tttgccgcag cgtattcgcc
180cgtcagcttc gaggtataac ggattgtagt tgcagctcgt cagtttgttg tgtacgacct
240ggcgtgtcaa tgaatgggtc atggtggtga cgatcccgcg aatctcagcc gttttctcgg
300gactgtagca gacttcgccg tccggacacc gcagcctgtg gattcatgaa aatctactct
360ggcattcccg aggatcgtcg atggaacatg gctatcagaa acgtcgagag acagatccag
420acgcaccaca gaacgcagac aatcatgaaa atacccccgg tactctgcgt tgttaccact
480gcttcccgcg tactctgcgt tgttaccact gcttgcccta tagtgagtcg tattagaagc
540cgaattc
54711253DNAHuman cytomegalovirus 11gaattcggct tctaatacga ctcactatag
ggcctggatc agtacctgga gagcgttagt 60gggcctggat cagtacctgg agagcgttag
tgggcctgga tcagtacctg gagagcgtta 120gtgggcctgg atcagtacct ggagagcgtt
agtgggcctg gatcagtacc tggagagcgt 180tagtgggcct ggatcagtac ctggagagcg
ttagtgggcc tggaagtacc tggagagcgt 240taaagccgaa ttc
25312614DNAHuman cytomegalovirus
12gaattcggct taacctctcc aggtactgat ccaggcccac gatccgggtt atcttgtcgt
60attccaggtt gatccatcga tagggaacgc tgccagcggc gcccagcagg tactgcgcct
120tgtcgttcac tttgccgcag cgtattcgcc cgtcagcttc gaggtataac ggattgtagt
180tgcagctcgt cagtttgttg tgtacgacct ggcgtgtcaa tgaatgggtc atggtggtga
240cgatcccgcg aatctcagcc gttttctcgg gactgtagca gacttcgccg tccggacacc
300gcagcctgtg gattcatgaa aatctactct ggcattcccg aggatcgtcg atggaacatg
360gctatcagaa acgtcgagag acagatccag acgcaccaca gaacgcagac aatcatgaaa
420atacgtacgc gacggtgaag cgattgcaca ttttgaaatc gtaacagcgt tccggcgggt
480ggttgacgtt tatgaattcg caacattctt ctgcgcgtac ccgcggcacg cggctgtgac
540ccaatagcag ccacaacgcc gtcaagaacg gcgtcaggtt tttgggactc atgacgcgcg
600gttttcaaaa ttcc
61413767DNAHuman cytomegalovirus 13gaattcggct ttaacgctct ccaggtactg
atccaggccc acgtcttccg ggactacagc 60gtgtcttttc aggtgcgatt gacgttcacc
gaggccaata accagactta caccttctgc 120acccatccca atctcatcgt ttgagcccgt
cgcgcgcgca tgaaaaccgc gcgtcatgag 180tcccaaaaac ctgacgccgt tcttgacggc
gttgtggctg ctattgggtc acagccgcgt 240gccgcgggta cgcgcagaag aatgttgcga
attcataaac gtcaaccacc cgccggaacg 300ctgttacgat ttcaaaatgt gcaatcgctt
caccgtcgcg tacgtatttt catgattgtc 360tgcgttctgt ggtgcgtctg gatctgtctc
tcgacgtttc tgatagccat gttccatcga 420cgatcctcgg gaatgccaga gtagattttc
atgaatccac aggctgcggt gtccggacgg 480cgaagtctgc tacagtcccg agaaaacggc
tgagattcgc gggatcgtca ccaccatgac 540ccattcattg acacgccagg tcgtacacaa
caaactgacg agctgcaact acaatccgtt 600atacctcgaa gctgacgggc gaatacgctg
cggcaaagtg aacgacaagg cgcagtacct 660gctgggcgcc gctggcagcg ttccctagat
ggatcaacct ggaatacgac aagataaccc 720ggatcgtggg cctggatcag tacctggaga
gcgttaaagc cgaattc 76714577DNAHuman cytomegalovirus
14gaattcggct taatacgact cactataggg caagcagtgg taacaacgca gagtacgcgg
60ggcagaagaa tgttgcgaat tcataaacgt caaccacccg ccggaacgct gttacgattt
120caaaatgtgc aatcgcttca ccgtcgcgta cgtattttca tgattgtctg cgttctgtgg
180tgcgtctgga tctgtctctc gacgtttctg atagccatgt tccatcgacg atcctcggga
240atgccagagt agattttcat gaatccacag gctgcggtgt ccggacggcg aagtctgcta
300cagtcccgag aaaacggctg agattcgcgg gatcgtcacc accatgaccc attcattgac
360acgccaggcc gtacacaaca aactgacgag ctgcaactac aatccgttat acctcgaagc
420tgacgggcga atacgctgcg gcaaagtgaa cgacaaggcg cagtacctgc tgggcgccgc
480tggcagcgtt ccctatcgat ggatcaacct ggaatacgac aagataaccc ggatcgtggg
540cctggatcag tacctggaga gcgttaaagc cgaattc
577151778DNAHuman cytomegalovirus 15ttgtgtcggg tgtggctgtc tgtttgtctg
tgcgccgtgg tgctgggtca gtgccagcgg 60gagaccgcag aaaaaaacga ttattaccga
gtaccgcatt actgggacgc gtgctctcgc 120gcgctgcctg accaaacccg ttacaagtat
gtggaacagc tcgtggacct cacgttgaac 180taccactacg atgcgagcca cggcttggac
aactttgacg tgctcaagag aatcaacgtg 240accgaggtgt cgttgctcat cagcgacttt
agacgtcaga accgtcgcgg cggcaccaac 300aaaaggacca cgttcaacgc cgccggttcg
ctggcgcctc acgcccggag cctcgagttc 360agcgtgcggc tctttgccaa ctagcctgcg
tcacgggaaa taatatgcta cggcttctgc 420ttcgtcacca ctttcactgc ctgcttctgt
gcgcggtttg ggcaacgccc tgtctggcgt 480ctccgtggtt cacgctaacg gcgaaccaga
atccgtcccc gccatggtct aaactgacgt 540atcccaaacc gcatgacgcg gcgacgtttt
actgtccttt tctctatccc tcgcccccac 600ggtccccctc gcaattcccg gggttccagc
gggtatcaac gggtcccgag tgtcgcaacg 660agaccctgta tctgctgtac aaccgggaag
gccagacctt ggtggagaga agctccacct 720gggtgaaaaa ggtgatctgg tatctgagcg
gtcgcaatca gaccatcctc caacggatgc 780cccgaacggc ttcgaaaccg agcgacggaa
acgtgcagat cagcgtggaa gacgccaaga 840tttttggagc gcacatggtg cccaagcaga
ccaagctgct acgtttcgtc gtcaacgatg 900gcacacgtta tcagatgtgt gtgatgaaac
tggagagctg ggcccacgtc ttccgggact 960acagcgtgtc ttttcaggtg cgattgacgt
tcaccgaggc caataaccag acttacacct 1020tctgcaccca tcccaatctc atcgtttgag
cccgtcgcgc gcgcagggaa ttttgaaaac 1080cgcgcgtcat gagtcccaaa aacctgacgc
cgttcttgac ggcgttgtgg ctgctattgg 1140gtcacagccg cgtgccgcgg gtacgcgcag
aagaatgttg cgaattcata aacgtcaacc 1200acccgccgga acgctgttac gatttcaaaa
tgtgcaatcg cttcaccgtc gcgtacgtat 1260tttcatgatt gtctgcgttc tgtggtgcgt
ctggatctgt ctctcgacgt ttctgatagc 1320catgttccat cgacgatcct cgggaatgcc
agagtagatt ttcatgaatc cacaggctgc 1380ggtgtccgga cggcgaagtc tgctacagtc
ccgagaaaac ggctgagatt cgcgggatcg 1440tcaccaccat gacccattca ttgacacgcc
aggtcgtaca caacaaactg acgagctgca 1500actacaatcc gttatacctc gaagctgacg
ggcgaatacg ctgcggcaaa gtgaacgaca 1560aggcgcagta cctgctgggc gccgctggca
gcgttcccta tcgatggatc aacctggaat 1620acgacaagat aacccggatc gtgggcctgg
atcagtacct ggagagcgtt aagaaacaca 1680aacggctgga tgtgtgccgc gctaaaatgg
gctatatgct gcagtgaata ataaaatgtg 1740tgtttgtccg aaaaaaaaaa aaaaaaaaaa
aaaaaaaa 1778161422DNAHuman cytomegalovirus
16gaattcggct ttctgcttcg tcaccacttt cactgcctgc ttctgtgcgc ggtttgggca
60acgccctgtc tggcgtctcc gtggttcacg ctaacggcga accagaatcc gtccccgcca
120tggtctaaac tgacgtatcc caaaccgcat gacgcggcga cgttttactg tccttttctc
180tatccctcgc ccccacggtc cccctcgcaa ttcccggggt tccagcgggt atcaacgggt
240cccgagtgtc gcaacgagac cctgtatctg ctgtacaacc gggaaggcca gaccttggtg
300gagagaagct ccacctgggt gaaaaaggtg atctggtatc tgagcggtcg caatcagacc
360atcctccaac ggatgccccg aacggcttcg aaaccgagcg acggaaacgt gcagatcagc
420gtggaagacg ccaagatttt tggagcgcac atggtgccca agcagaccaa gctgctacgt
480ttcgtcgtca acgatggcac acgttatgtg tgatgaaact ggagagctgg gcccacgtct
540tccgggacta cagcgtgtct tttcaggtgc gattgacgtt caccgaggcc aataaccaga
600cttacacctt ctgcacccat cccaatctca tcgtttgagc ccgtcgcgcg cgcagggaat
660tttgaaaacc gcgcgtcatg agtcccaaaa acctgacgcc gttcttgacg gcgttgtggc
720tgctattggg tcacagccgc gtgccgcggg tacgcgcaga agaatgttgc gaattcataa
780acgtcaacca cccgccggaa cgctgttacg atttcaaaat gtgcaatcgc ttcaccgtcg
840cgtacgtatt ttcatgattg tctgcgttct gtggtgcgtc tggatctgtc tctcgacgtt
900tctgatagcc atgttccatc gacgatcctc gggaatgcca gagtagattt tcatgaatcc
960acaggctgcg gtgtccggac ggcgaagtct gctacagtcc cgagaaaacg gctgagattc
1020gcgggatcgt caccaccatg acccattcat tgacacgcca ggtcgtacac aacaaactga
1080cgagctgcaa ctacaatccg ttatacctcg aagctgacgg gcgaatacgc tgcggcaaag
1140tgaacgacaa ggcgcagtac ctgctgggcg ccgctggcag cgttccctat cgatggatca
1200acctggaata cgacaagata acccggatcg tgggcctgga tcagtacctg gagagcgtta
1260agaaacacaa acggctggat gtgtgccgcg ctaaaatggg ctatatgctg cagtgaataa
1320taaaatgtgt gtttgtccaa aaaaaaaaaa aaaaaaaaaa aaaagtactc tgcgttgtta
1380ccactgcttg ccctatagtg agtcgtatta gaagccgaat tc
142217510DNAHuman cytomegalovirus 17gaattcggct tctaatacga ctcactatag
ggcaagcagt ggtaacaacg cagagtacgc 60ggggactgtc cttttctcta tccctcgccc
ccacggtccc cctcgcaatt cccggggttc 120cagcgggtat caacgggtcc cgagtgtcgc
aacgagaccc tgtatctgct gtacaaccgg 180gaaggccaga ccttggtgga gagaagctcc
acctgggtga aaaaggtgat ctggtatctg 240agcggtcgca atcagaccat cctccaacgg
atgccccgaa cggcttcgaa accgagcgac 300ggaaacgtgc agatcagcgt ggaagacgcc
aagatttttg gagcgcacat ggtgcccaag 360cagaccaagc tgctacgttt cgtcgtcaac
gatggcacac gttatcagat gtgtgtgatg 420aaactggaga gctgggccca cgtcttccgg
gactacagcg tgtcttttca ggtgcgattg 480acgttcaccg aggccaataa agccgaattc
51018686DNAHuman cytomegalovirus
18gaattcggct tctaatacga ctcactatag ggcaagcagt ggtaacaacg cagagtacgc
60ggggcactac gatgcgagcc acggcttgga caactttgac gtgctcaaga gaatcaacgt
120gaccgaggtg tcgttgctca tcagcgactt tagacgtcag aaccatcgcg gcggcaccaa
180caaaaggacc acgttcaacg ccgccggttc gctggcgcct cacgcccgga gcctcgagtt
240cagcgtgcgg ctccttgcca actagcctgc gtcacgggaa ataatatgct acggcttctg
300cttcgtcacc actttcactg cctgcttctg tgcgcggttt gggcaacgcc ctgtctggcg
360tctccgtggt tcacgctaac ggcgaaccag aatccgtccc cgccatggtc taaactgacg
420tatcccaaac cgcatgacgc ggcgacgttt tgctgtcctt ttctctatcc ctcgccccca
480cggtccccct cgcaattccc ggggttccag cgggtatcaa cgggtcccga gtgtcgcaac
540gagaccctgt atctgctgta caaccgggaa ggccagacct tggtggagag aagctccacc
600tgggtgaaaa aggtgatctg gtatctgagc ggtcgcaatc agaccatcct ccaacggatg
660ccccgaacgg cttcgaaacc gagcga
68619670DNAHuman cytomegalovirus 19gaattcggct tctaatacga ctcactatag
ggcaagcagt ggtaacaacg cagagtacgc 60ggggagaacc gtcgcggcgg caccaacaaa
aggaccacgt tcaacgccgc cggttcgctg 120gcgcctcacg cccggagcct cgagttcagc
gtgcggctct ttgccaacta gcctgcgtca 180cgggaaataa tatgctacgg cttctgcttc
gtcaccactt tcactgcctg cttctgtgcg 240cggtttgggc aacgccctgt ctggcgtctc
cgtggttcac gctaacggcg aaccagaatc 300cgtccccgcc atggtctaaa ctgacgtatc
ccaaaccgca tgacgcggcg acgttttact 360gtccttttct ctatccctcg cccccacggt
ccccctcgca attcccgggg ttccagcggg 420tatcaacggg tcccgagtgt cgcaacgaga
ccctgtatct gctgtacaac cgggaaggcc 480agaccttggt ggagagaagc tccacctggg
tgaaaaaggt gatctggtat ctgagcggtc 540gcaatcagac catcctccaa cggatgcccc
gaacggcttc gaaaccgagc gacggaaacg 600tgcagatcag cgtggaagac gccaagattt
ttggagcgca catggtgccc aagcagacca 660agctgctacg
67020226DNAHuman cytomegalovirus
20gaattcggct tctaatacga ctcactatag ggcaagcagt ggtaacaacg cagagtactt
60tttttttttt tttttttttt ttttttggga tacgtcagtt tagaccatgg cggggacgga
120ttctggttcg ccgttagcgt gaaccacgga gacgccagac agggcgttgc ccaaaccgcg
180cacagaagca ggcagtgaag tggtgacgaa gcagaaagcc gaattc
22621653DNAHuman cytomegalovirus 21gaattcggct ttctgcttcg tcaccacttc
actgcctgct tctgtgcgcg gtttgggcaa 60cgccctgtct ggcgtctccg tggttcacgc
taacggcgaa ccagaatccg tccccgccat 120ggtctaaact gacgtatccc aaaccgcatg
acgcggcgac gttttactgt ccttttctct 180atccctcgcc cccacggtcc ccctcgcaat
tcccggggtt ccagcgggta tcaacgggtc 240ccgagtgtcg caacgagacc ctgtatctgc
tgtacaaccg ggaaggccag accttggtgg 300agagaagctc cacctgggtg aaaaaggtga
tctggtatct gagcggtcac aatcagacca 360tcctccaacg gatgccccga acggcttcga
aaccgagcga cggaaacgtg cagatcagcg 420tggaagacgc caagattttt ggagcgcaca
tggtgcccaa gcagaccaag ctgctacgtt 480tcgtcgtcaa cgatggcaca cgttatcaga
tgtgtgtgat gaaactggag agctgggccc 540acgtcttccg ggactacgac aagataaccc
ggatcgtggg cctggatcag tacctggaga 600gcgttaagaa acacaaacgg ctggatgtgt
gccgcgctaa aatgggctat atg 65322607DNAHuman cytomegalovirus
22gaattcggct tcgcagaaga atgttgcgaa ttcataaacg tcaaccaccc gccggaacgc
60tgttacgatt tcaaaatgtg caatcgcttc accgtcgcgt acgtattttc atgattgtct
120gcgttctgtg gtgcgtctgg atctgtctct cgacgtttct gatagccatg ttccatcgac
180gatcctcggg aatgccagag tagattttca tgaatccaca ggctgcggtg tccggacggc
240gaagtctgct acagtcccga gaaaacggct gagattcgcg ggatcgtcac caccatgacc
300cattcattga cacgccaggt cgtacacaac aaactgacga gctgcaacta caatccgtta
360tacctcgaag ctgacgggcg aatacgctgc ggcaaagtga acgacaaggc gcagtacctg
420ctgggcgccg ctggcagcgt tccctatcga tggatcaacc tggaatacga caagataacc
480cggatcgtgg gcctggatca gtacctggag agcgttaaga aacacaaacg gctggatgtg
540tgccgcgcta aaatgggcta tatgctgcag tgaataataa aatgtgtgtt tgtccggaaa
600aaaaaaa
60723658DNAHuman cytomegalovirus 23gaattgtctg cttcgtcacc atttcactgc
ctgcttctgt gcgcggtttg ggcaacgccc 60tgtctggcgt ctccgtggtt cacgctaacg
gcgaaccaga atccgtcccc gccatggtct 120aaactgacgt atcccaaacc gcatgacgcg
gcgacgtttt actgtccttt tctctatccc 180tcgcccccac ggtccccctc gcaattcccg
gggttccagc gggtatcaac gggtcccgag 240tgtcgcaacg agaccctgta tctgctgtac
aaccgggaag gccagacctt ggtggagaga 300agctccacct gggtgaaaaa ggtgatctgg
tatctgagcg gtcgcaatca gaccatcctc 360caacggatgc cccgaacggc ttcgaaaccg
agcgacggaa acgtgcagat cagcgtggaa 420gacgccaaga tttttggagc gcacatggtg
cccaagcaga ccaagctgct acgtttcgtc 480gtcaacgatg gcacacgtta tcagatgtgt
gtgatgaaac tggagagctg ggcccacgtc 540ttccgggact acagcgtgtc ttttcaggtg
cgattgacgt tcaccgaggc caataaccag 600acttacacct tctgcaccca tcccaatctc
atcgtttgag cccgtcgcgc gcgcaggg 65824503DNAHuman cytomegalovirus
24gaattcggct tctaatacga ctcactatag ggcaagcagc ggtaacaacg cagagtactt
60tttttttttt tttttttttt tttttttgga caaacacaca gtttattatt cactgcagca
120tatagcccat tttagcgcgg cacacatcca gccgtttgtg tttcttaacg ctctccaggt
180actgatccag gcccacgatc cgggttatct tgtcgtattc caggttgatc catcgatagg
240gaacgctgcc agcggcgccc agcaggtact gcgccttgtc gttcactttg ccgcagcgta
300ttcgcccgtc agcttcgagg tataacggat tgtagttgca gctcgtcagt ttgttgtgta
360cgacctggcg tgtcaatgaa tgggtcatgg tggtgacgat cccgcgaatc tcagccgttt
420tctcgggact gtagcagact tcgccgtccg gacaccgcag caagccgaat tccagcacac
480tggcggccgt tactagtgga tcc
50325636DNAHuman cytomegalovirus 25gaattcggct tctaatacga ctcactatag
ggcaagcagt ggtaacaacg cagagtacgc 60gggggaccat cctccaacgg atgccccgaa
cggcttcgaa accgagcgac ggaaacgtgc 120agatcagcgt ggaagacgcc aagatttttg
gagcgcacat ggtgcccaag cagaccaagc 180tgctacgttt cgtcgtcaac gatggcacac
gttatcagat gtgtgtgatg aaactggaga 240gctgggccca cgtcttccgg gactacagcg
tgtcttttca ggtgcgattg acgttcaccg 300aggccaataa ccagacttac accttctgca
cccatcccaa tctcatcgtt tgagcccgtc 360gcgcgcgcag ggaattttga aaaccgcgcg
tcatgagtcc caaaaacctg acgccgttct 420tgacggcgtt gtggctgcta ttgggtcaca
gccgcgtgcc gcgggtacgc gcagaagaat 480gttgcgaatt cataaacgtc aaccacccgc
cggaacgctg ttacgatttc aaaatgtgca 540atcgcttcac cgtcgcgtac gtattttcat
gattgtctgc gttctgtggt gcgtctggat 600ctgtctctcg acgtttctga tagccatgtt
ccatcg 636261432DNAHuman cytomegalovirus
26gaattcggct ttctgcttcg tcaccacttt cactgcctgc ttctgtgcgc ggtttgggca
60acgccctgtc tggcgtctcc gtggttcacg ctaacggcga accagaatcc gtccccgcca
120tggtctaaac tgacgtatcc caaaccgcat gacgcggcga cgttttactg tccttttctc
180tatccctcgc ccccacggtc cccctcgcaa ttcccggggt tccagcgggt atcaacgggt
240cccgagtgtc gcaacgagac cctgtatctg ctgtacaacc gggaaggcca gaccttggtg
300gagagaagct ccacctaggt gaaaaaggtg atctggtatc tgagcggtcg caatcagacc
360atcctccaac ggatgccccg aacggcttcg aaaccgagcg acggaaacgt gcagatcagc
420gtggaagacg ccaagatttt tggagcgcac atggtgccca agcagaccaa gctgctacgt
480ttcgtcgtca acgatggcac acgttatcag atgtgtgtga tgaaactgga gagctgggcc
540cacgtcttcc gggactacag cgtgtctttt caggtgcgat tgacgttcac cgaggccaat
600aaccagactt acaccttctg cacccatccc aatctcatcg tttgagcccg tcgcgcgcgc
660agggaatttt gaaaaccgcg cgtcatgagt cccaaaaacc tgacgccgtt cttgacggcg
720ttgtggctgc tattgggtca cagccgcgtg ccgcgggtac gcgcagaaga atgttgcgaa
780ttcataaacg tcaaccaccc gccggaacgc tgttacgatt tcaaaatgtg caatcgcttc
840accgtcgcgt acgtattttc atgattgtct gcgttctgtg gtgcgtctgg atctgtctct
900cgacgtttct gatagccatg ttccatcgac gatcctcggg aatgccagag tagattttca
960tgaatccaca ggctgcggtg tccggacggc gaagtctgct acagtcccga gaaaacggct
1020gagattcgcg ggatcgtcac caccatgacc cattcattga cacgccaggt cgtacacaac
1080aaactgacga gctgcaacta caatccgtta tacctcgaag ctgacgggcg aatacgctgc
1140ggcaaagtga acgacaaggc gcagtacctg ctgggcgccg ctggcagcgt tccctatcga
1200tggatcaacc tggaatacga caagataacc cggatcgtgg gcctggatca gtacctggag
1260agcgttaaga aacacaaacg gctggatgtg tgccgcgcta aaatgggcta tatgctgcag
1320tgaataataa aatgtgtgtt tgtccaaaaa aaaaaaaaaa aaaaaaaaaa aaaagtactc
1380tgcgttgtta ccactgcttg ccctatagtg agtcgtatta gaagccgaat tc
143227880DNAHuman cytomegalovirus 27taacgctctc caggtactga tccaggccca
cgatccgggt tatcttgtcg tattccaggt 60tgatccatcg atagggaacg ctgccagcgg
cgcccagcag gtactgcgcc ttgtcgttca 120ctttgccgca gcgtattcgc ccgtcagctt
cggggtataa cctacaacac ggaggggaag 180gggggtacaa aacgtgaaat tagacttttt
tttttttaat gatgttttgt ccctctctgt 240cttactctcc cataggctgt aaggccctag
aggaagagac ttacggattg tagttgcagc 300tcgtcagttt gttgtgtacg acctggcgtg
tcaatgaatg ggtcatggtg gtgacgatcc 360cgcgaatctc agccgttttc tcgggactgt
agcagacttc gccgtccgga caccgcagcc 420tgtggattca tgaaaatcta ctctggcatt
cccgaggatc gtcgatggaa catggctatc 480agaaacgtcg agagacagat ccagacgcac
cacagaacgc agacaatcat gaaaatacgt 540acgcgacggt gaagcgattg cacattttga
aatcgtaaca gcgttccggc gggtggttga 600cgtttatgaa ttcgcaacat tcttctgcgc
gtacccgcgg cacgcggctg tgacccaata 660gcagccacaa cgccgtcaag aacggcgtca
ggtttttggg actcatgacg cgcggttttc 720aaaattccct gcgcgcgcga cgggctcaaa
cgatgagatt gggatgggtg cagaaggtgt 780aagtctggtt attggcctcg gtgaacgtca
atcgcacctg aaaagacgcg ctgtagtccc 840ggaagacgtg ggcctggatc agtacctgga
gagcgttaga 88028417DNAHuman cytomegalovirus
28gaattcggct tctaatacga ctcactatag ggcaagcagt ggtaacaacg cagagtacgc
60ggggaccctg tatctgctgt acaaccggga aggccagacc ttggtggaga gaagctccac
120ctgggtgaaa aaggtgatct ggtatctgag cggtcgcaat cagaccatcc tccaacggat
180gccccgaacg gcttcgaaac cgagcgacgg aaacgtgcag atcagcgtgg aagacgccaa
240gatttttgga gcgcacgtgg tgcccaagca gaccaagctg ctacgtttcg tcgtcaacga
300tggcacacgt tatcagatgt gtgtgatgaa actggagagc tgggcccacg tcttccggga
360ctacagcgtg tcttttcagg tgcgattacg ttcaccgagg ccaataaagc cgaattc
4172990DNAArtificial Sequenceprimer 29cgctgtaggg ataaatagtg cgatggcgtt
tgtgggagaa cgcagtagcg atgggttgcg 60acgtgcaccg atttattcaa caaagccacg
903087DNAArtificial Sequenceprimer
30aacggcgtca ggtctttggg actcatgacg cgcggttttc aaaattccct gcgcgcgcga
60cgggcgccag tgttacaacc aattaac
873188DNAArtificial Sequenceprimer 31aaaccacgtc ctcgtcacac gtcgttcgcg
gacatagcaa gaaatccacg tcgccacatc 60tcgagacgat ttattcaaca aagccacg
883287DNAArtificial Sequenceprimer
32gccagtggta ccacttgagc atcctggcca gaagcacgtc gggcgtcatc cccgagtcat
60agtagcgatt tattcaacaa agccacg
873387DNAArtificial Sequenceprimer 33acacatcgca cacagacttt ataaaccgta
gttgtcggcg ccatctagac tcactttatt 60gaaagccagt gttacaacca attaacc
873481DNAArtificial Sequenceprimer
34gcgccacacg cccggagcct cgagttcagc gtgcggctct ttgccaacta gcctgcgtca
60cggcgattta ttcaacaaag c
813583DNAArtificial Sequenceprimer 35cccggagcct cgagttcagc gtgcggctct
ttgccaacta gcctgcgtca cgggaaataa 60tcgatttatt caacaaagcc acg
833676DNAArtificial Sequenceprimer
36tgtctttcgg ttccaactct ttccccgccc catcacctcg cctgtactat gtgtcgattt
60attcaacaaa gccacg
763774DNAArtificial Sequenceprimer 37gctagttggc aaagagccgc acgctgaact
cgaggctccg ggcgtgtggc ggccagtgtt 60acaaccaatt aacc
743878DNAArtificial Sequenceprimer
38atgagacatc atacacatag tacaggcgag gtgatggggc ggggaaagag ttggaaccga
60aaggccagtg ttacaacc
783987DNAArtificial Sequenceprimer 39gcacccatcc caatctcatc gtttgagccc
gtcgcgcgcg cagggaattt tgaaaaccgc 60gcgtccgatt tattcaacaa agccacg
874087DNAArtificial Sequenceprimer
40tcgcgcgaca tgaatttagt cggcgacaga aatctcgaaa cgcgtatttc ggacaaacac
60acatgccagt gttacaacca attaacc
874182DNAArtificial Sequenceprimer 41tgcgttctgt ggtgcgtctg gatctgtctc
tcgacgtttc tgatagccat gttccatcga 60cgatttattc aacaaagcca cg
824281DNAArtificial Sequenceprimer
42cggcacacat ccagccgttt gtgtttctta acgctctcca ggtactgatc caggcccacg
60gccagtgtta caaccaatta a
814330DNAArtificial Sequenceprimer 43cggcacacat ccagccgttt gtgtttctta
304430DNAArtificial Sequenceprimer
44taacgctctc caggtactga tccaggccca
304530DNAArtificial Sequenceprimer 45tcgtcagttt gttgtgtacg acctggcgtg
304630DNAArtificial Sequenceprimer
46tattggcctc ggtgaacgtc aatcgcacct
304730DNAArtificial Sequenceprimer 47tgtgtcgggt gtggctgtct gtttgtctgt
304831DNAArtificial Sequenceprimer
48tctgcttcgt caccactttt cactgcctgc t
314930DNAArtificial Sequenceprimer 49cgcagaagaa tgttgcgaat tcataaacgt
305030DNAArtificial Sequenceprimer
50gctgcggtgt ccggacggcg aagtctgcta
305130DNAArtificial Sequenceprimer 51ccagctggca gattcccaaa ctaatgaaag
30521245DNAHuman cytomegalovirus
52ctaatacgac tcactatagg gcaagcagtg gtaacaacgc agagtacgcg gggagaatcc
60gtccccgcca tggtctaaac tgacgtatcc caaaccgcat gacgcggcga cgttttactg
120tccttttctc tatccctcgc ccccacggtc cccctcgcaa ttcccggggt tccagcgggt
180atcaacgggt cccgagtgtc gcaacgagac cctgtatctg ctgtacaacc gggaaggcca
240gaccttggtg gagagaagct ccacctgggt gaaaaaggtg atctggtatc tgagcggtcg
300caatcagacc atcctccaac ggatgccccg aacggcttcg aaaccgagcg acggaaacgt
360gcagatcagc gtggaagacg ccaagatttt tggagcgcac atggtgccca agcagaccaa
420gctgctacgt ttcgtcgtca acgacggcac acgttatcag atgtgtgtga tgaaactgga
480gagctgggcc cacgtcttcc gggactacag cgtgtctttt caggtgcgat tgacgttcac
540cgaggccaat aaccagactt acaccttctg cacccatccc aatctcatcg tttgagcccg
600tcgcgcgcgc agggaatttt gaaaaccgcg cgtcatgagt cccaaaaacc tgacgccgtt
660cttgacggcg ttgtggctgc tattgggtca cagccgcgtg ccgcgggtac gcgcagaaga
720atgttgcgaa ttcataaacg tcaaccaccc gccggaacgc tgttacgatt tcaaaatgtg
780caatcgcttc accgtcgcgt acgtattttc atgattgtct gcgttctgtg gtgcgtctgg
840atctgtctct cgacgtttct gatagccatg ttccatcgac gatcctcggg aatgccagag
900tagattttca tgaatccaca ggctgcggtg tccggacggc gaagtctgct acagtcccga
960gaaaacggct gagattcgcg ggatcgtcac caccatgacc cattcattga caccccaggt
1020cgtacacaac aaactgacga gctgcaacta caatccgtta tacctcgaag ctgacgggcg
1080aatacgctgc ggcaaagtga acgacaaggc gcagtacctg ctgggcgccg ctggcagcgt
1140tccctatcga tggatcaacc tggaatacga caagataacc cggatcgtgg gcctggatca
1200gtacctggag agcgttaaga aacacaaacg gctggatgtg tgccg
124553568DNAHuman cytomegalovirus 53gctgctattg ggtcacagcc gcgtgccgcg
ggtacgcgca gaagaatgtt gcgaattcat 60aaacgtcaaa cacccgccgg aacgctgtta
cgatttcaaa atgtgcaatc gcttaccgtc 120gcgtacgtat tttcatgatc gtctgcgttc
tgtggtgcgt ctggatctgt ctctcgacgt 180ttctgatagc catgttccat cgacgatccc
cgggaatgcc agagtagatt ttcatgaatc 240cacaggctgc ggtgtccgga cggcgaagtc
tgctacagtc ccgagaaaac ggctgagatt 300cgcgggatcg tcaccaccat acccattcat
tgacacgcca ggtcgtacac aacaaactga 360cgagctgcaa ctacaatccg ttatacctcg
aagctcacgg gcgaatacgc tgcggcaaag 420tgaacgacaa ggcgcagtac ctgctgggcg
ccgctggcag cgttccctat cgatggatca 480acctggaata cgacaagata acccggatcg
tgggcctgga tcagtacctg gagagcgtta 540agaaacacaa acggctggat gtgtgccg
56854787DNAHuman cytomegalovirus
54ctaatacgac tcactatagg gcaagcagtg gtaacaacgc agagtacgcg ggggaccatc
60ctccaacgga tgccccgaac ggcttcgaaa ccgagcgacg gaaacgtgca gatcagcgtg
120gaagacgcca agatttttgg agcgcacatg gtgcccaagc agaccaagct gctacgtttc
180gtcgtcaacg atggcacacg ttatcagatg tgtgtgatga aactggagag ctgggcccac
240gtcttccggg actacagcgt gtcttttcag gtgcgattga cgttcaccga ggccaataac
300cagacttaca ccttctgcac ccatcccaat ctcatcgttt gagcccgtcg cgcgcgcagg
360gaattttgaa aaccgcgcgt catgagtccc aaaaacctga cgccgttctt gacggcgttg
420tggctgctat tgggtcacag ccgcgtgccg cgggtacgcg cagaagaatg ttgcgaattc
480ataaacgtca accacccgcc ggaacgctgt tacgatttca aaatgtgcaa tcgcttcacc
540gtcgcgtacg tattttcatg attgtctgcg ttctgtggtg cgtctggatc tgtctctcga
600cgtttctgat agccatgttc catcgacgat cctcgggaat gccagagtag attttcatga
660atccacaggc tgcggtgtcc ggacggcgaa gtctgctaca gtcccgagaa aacggctgag
720attcgcggga tcgtcaccac catgacccat tcattgacac gccaggtcgt acacaacaaa
780ctgacga
787551292DNAHuman cytomegalovirus 55tctgcttcgt caccatttca ctgcctgctt
ctgtgcgcgg tttgggcaac gccctgtctg 60gcgtctccgt ggttcacgct aacggcgaac
cagaatccgt ccccgccatg gtctaaactg 120acgtatccca aaccgcatga cgcggcgacg
ttttactgtc cttttctcta tccctcgccc 180ccacggtccc cctcgcaatt cccggggttc
cagcgggtat caacgggtcc cgagtgtcgc 240aacgagaccc tgtatctgct gtacaaccgg
gaaggccaga ccttggtgga gagaagctcc 300acctgggtga aaaaggtgat ctggtatctg
agcggtcgca atcagaccat cctccaacgg 360atgccccgaa cggcttcgaa accgagcgac
ggaaacgtgc agatcagcgt ggaagacgcc 420aagatttttg gagcgcacat ggtgcccaag
cagaccaagc tgctacgttt cgtcgtcaac 480gatggcacac gttatcagat gtgtgtgatg
aaactggaga gctgggccca cgtcttccgg 540gactacagcg tgtcttttca ggtgcgattg
acgttcaccg aggccaataa ccagacttac 600accttctgca cccatcccaa tctcatcgtt
tgagcccgtc gcgcgcgcag ggaattttga 660aaaccgcgcg tcatgagtcc caaaaacctg
acgccgttct tgacggcgtt gtggctgcta 720ttgggtcaca gccgcgtgcc gcgggtacgc
gcagaagaat gttgcgaatt cataaacgtc 780aaccacccgc cggaacgctg ttacgatttc
aaaatgtgca atcgcttcac cgtcgcgctg 840cggtgtccgg acggcgaagt ctgctacagt
cccgagaaaa cggctgagat tcgcgggatc 900gtcaccacca tgacccattc attgacacgc
caggtcgtac acaacaaact gacgagctgc 960aactacaatc cgttatacct cgaagctgac
gggcgaatac gctgcggcaa agtgaacgac 1020aaggcgcaac aaggcgcagt acctgctggg
cgccgctggc agcgttccct atcgatggat 1080caacctggaa tacgacaaga taacccggat
cgtgggcctg gatcagtacc tggagagcgt 1140taagaaacac aaacggctgg atgtgtgccg
cgctaaaatg ggctatatgc tgcagtgaat 1200aataaaatgt gtgtttgtac aaaaaaaaaa
aaaaaaaaaa aaaaagtact ctgcgttgtt 1260accactgctt gccctatagt gagtcgtatt
ag 1292567650DNAHuman cytomegalovirus
56actgtggctg gaaactggtt acctgtgaag atggctaact atcctgttct gtcctggaaa
60aacttttggc gtcgtaggtg gactttgcag tatgcgggtt agtgaagtta tgtcatttat
120ttacgtttac gatctcgtat tacaaaccgc ggagaggatg ataccgttcg gccccatgag
180ttatttttat tcttccggta ggaggcatga agcctctgat aatgctcatc tgctttgctg
240tgatattatt gcagcttgga gtgactaaag tgtgtcagca taatgaagtg caactgggca
300atgagtgctg ccctccgtgt ggttcgggac aaagagttac taaagtatgc acggattata
360ccagtgtaac gtgtacccct tgccccaacg gcacgtatgt atcgggactt tacaactgta
420ccgattgcac tcaatgtaac gtcactcagg tcatgattcg taactgcact tccaccaata
480ataccgtatg cgcacctaag aaccatacgt acttttccac tccaggcgtc caacatcaca
540aacaacgaca gcaaaatcat accgcacata taaccgtcaa acaaggaaaa agcggtcgtc
600atactctagc ctggttgtct ctctttatct ttcttgtggg tatcatactt ttaattctct
660atcttatagc cgcctatcgg agtgagagat gccaacagtg ttgctcaatc ggcaaaattt
720tctaccgcac cctgtaagct tcctgttgtt gtttttacat cacggtacga tgaagtcaca
780cagataatta cagatgagct gttcatattt tttattattt tttccaattc ctgcactaaa
840aaaagaagca ctttacggaa ccgtgtctga gtatctgtgg ggaatttagg tactttttgc
900cgacgtcagg aaaaataagt gtcgcctaca taagagcccg gtgctatcgt gctgtcactc
960tttcttgttg ccttcgatgt acggcgtcct ggctcattac tactccttca tcagtagccc
1020cagcgttatg gttaatttta agcatcataa cgccgtgcag ctgttatgtg cacggacccg
1080agacgcactg ccggatggga acgtttaacc catcatgcgt cgtatcacgc gaactacggg
1140gcatacgccg tgttgatggc tacatcgcaa agaaagtccc tagtgttaca tcgatacagt
1200gccgtgacag ccgtggccct gcagctcatg cctgttgaga tcgtccgcaa gctagatcag
1260tcggactggg tgcggggtgc ctggatcgtg tcagagactt ttccaactag cgaccccaaa
1320ggagtttgga gcgacgatga ctcctcgatg ggtggaagtg atgattgatg atgagaacct
1380gacaagaaag acgagagaga aatttagagc tgtcattgta gaattagtct agattcctga
1440taataaacag tatcgatttt gaaacctaat tgacgtgtga tcgattttta aacctctgtg
1500ttgtgtgatt gattggtatg tggggggatc cgatttcaaa ggggggtact tatcgggaat
1560tgatgtgtca tggacgcagt tttgagcgat tttccgggaa taccggatat tacgaattac
1620tggtagtgac gtagataata aaattataat gcgattaatt tttggtgcgt tgattatttt
1680tttagcatat gtgtatcatt atgaggtgaa tggaacagaa ttacgctgca gatgtcttca
1740tagaaaatgg ccgcctaata aaattatatt gggtaattat tggcttcatc gcgatcccag
1800agggcccgga tgcgataaaa atgaacattt attgtatcca gacggaagga aaccgcctgg
1860acctggagta tgtttatcgc ccgatcacct cttctcaaaa tggttagaca aacacaacga
1920taataggtgg tataatgtta acataacgaa atcaccagga ccgagacgaa taaatataac
1980cttgataggt gttagaggat aatatttaat gtatgttttc aaacagacaa gttcgttaaa
2040acaaaatatt acagtatgtg tttaatatgg tgctaacatg gttgcaccat ccggtttcaa
2100actcgcatat caatctgtta tcggtacgac acctgtcatt aatcgcatat atgttactta
2160ccatatgtcc cctagccgtc catgttttag aactagaaga ttacgacagg cgctgccgtt
2220gcaacaacca aattctgttg aataccctgc cggtcggaac cgaattgctt aagccaatcg
2280cagcgagcga aagctgcaat cgtcaggaag tgctggctat tttaaaggac aagggaacca
2340agtgtctcaa tcctaacgcg caagccgtgc gtcgtcacat caaccggcta ttttttcggt
2400taatcttaga cgaggaacaa cgcatttacg acgtagtgtc taccaatatt gagttcggtg
2460cctggccagt ccctacggcc tacaaagcct ttctttggaa atacgccaag agactgaact
2520accaccactt cagactgcgc tggtgatcat gtccctattt taccgtgcgg tagctctggg
2580cacgctaagc gctttggtgt ggtacagcac tagcatcctc gcagagatta acgaaaattc
2640ctgctcctca tcttctgcgg atcacgaaga ctgcgaggaa ccggacgaga tcgttcgcga
2700agagcaagac tatcgggctc tgctggcctt ttccctagtg atttgcggta cgctcctcgt
2760cacttgtgtg atctgagacg tcatgctggt agcgtttatg agtcgggcgg tggccgacac
2820gccgcatttc ctaacccgcg cagcatgttg cgcttgctgt tcacgctcgt cctgctggcc
2880ctccacgggc agtctgtcgg cgctagccgc gactatgtgc atgttcggct actgagctac
2940cgaggcgacc ccctggtctt caagcacact ttctcgggtg tgcgtcgacc cttcaccgag
3000ctaggctggg ctgcgtgtcg cgactgggac agtatgcatt gcacaccctt ctggtctacc
3060gatctggagc agatgaccga ctcggtgcgg cgttacagca cggtgagccc cggcaaggaa
3120gtgacgcttc agcttcacgg gaaccaaacc gtacagccgt cgtttctaag ctttacgtgc
3180cgcctgcagc tagaacccgt ggtggaaaat gttggcctct acgtggccta cgtggtcaac
3240gacggcgaac gcccacaaca gttttttaca ccgcaggtag acgtggtacg ctttgctcta
3300tatctagaaa cactctcccg gatcgtggaa ccgttagaat caggtcgcct ggcagtggaa
3360tttgatacgc ctgacctagc tctggcgccc gatttagtaa gcagcctctt cgtggccgga
3420cacggcgaga ccgactttta catgaactgg acgctgcgtc gcagtcagac ccactacctg
3480gaggagatgg ccttacaggt ggagattcta aaaccccgcg gcgtacgtca ccgcgctatt
3540atccaccatc cgaagctaca gccgggcgtt ggcctgtgga tagatttctg cgtgtaccgc
3600tacaacgcgc gcctgacccg cggctacgta cgatacaccc tgtcaccgaa agcgcgcttg
3660cccgcaaaag cagagggttg gctggtgtca ctagacagat tcatcgtgca gtacctcaac
3720acattgctga ttacaatgat ggcggcgata tgggctcgcg ttttgataac ctacctggtg
3780tcgcggcgtc ggtagaggct tgcggaaacc acgtcctcgt cacacgtcgt tcgcggacat
3840agcaagaaat ccacgtcgcc acatctcgag aatgccggcc ttgcggggtc cccttcgcgc
3900aacattcctg gccctggtcg cgttcgggtt gctgcttcag atagacctca gcgacgctac
3960gaatgtgacc agcagcacaa aagtccctac tagcaccagc aacagaaata acgtcgacaa
4020cgccacgagt agcggaccca caaccgggat caacatgacc accacccacg agtcttccgt
4080tcacaacgtg cgcaataacg agatcatgaa agtgctggct atcctcttct acatcgtgac
4140aggcacctcc attttcagct tcatagcggt actgatcgcg gtagtttact cctcgtgttg
4200caagcacccg ggccgctttc gtttcgccga cgaagaggcc gtcaacctgt tggacgacac
4260ggacgacagt ggcggcagca gcccgtttgg cagcggttcc cgacgaggtt ctcagatccc
4320cgccggattt tgttcctcga gcccttatca gcggttggaa actcgggact gggacgagga
4380ggaggaggcg tccgcggccc gcgagcgcat gaaacatgat cctgagaacg tcatctattt
4440cagaaaggat ggcaacttgg acacgtcgtt cgtgaatccc aattatggga gaggctcgcc
4500tttgaccatc gaatctcacc tctcggacaa tgaggaggac cccatcaggt actacgtttc
4560ggtgtacgat gaactgaccg cctcggaaat ggaagaacct tcgaacagca ccagctggca
4620gattcccaaa ctaatgaaag ttgccatgca acccgtctcg ctcagagatc ccgagtacga
4680ctaggctttt ttttttgtct ttcggttcca actctttccc cgccccatca cctcgcctgt
4740actatgtgta tgatgtctca taataaagct ttctttctca gtctgcaaca tgcagctgtg
4800tcgggtgtgg ctgtctgttt gtctgtgcgc cgtggtgctg ggtcagtgcc agcgggaaac
4860cgcggaaaaa aacgattatt accgagtacc gcattactgg gacgcgtgct ctcgcgcgct
4920gcccgaccaa acccgttaca agtatgtgga acagctcgtg gacctcacgt tgaactacca
4980ctacgatgcg agccacggct tggacaactt tgacgtgctc aagaggtgag ggtacgcgct
5040aaaggtgcat gacaacggga aggtaagggc gaacgggtaa cggctaagta accgcatggg
5100gtatgaaatg acgtttggaa cctgtgcttg cagaatcaac gtgaccgagg tgtcgttgct
5160catcagcgac tttagacgtc agaaccgtcg cggcggcacc aacaaaagga ccacgttcaa
5220cgccgccggt tcgctggcgc cacacgcccg gagcctcgag ttcagcgtgc ggctctttgc
5280caactagcct gcgtcacggg aaataatatg ctgcggcttc tgcttcgtca ccactttcac
5340tgcctgcttc tgtgcgcggt ttgggcaacg ccctgtctgg cgtctccgtg gtcgacgcta
5400acggcaaacc agaatccgtc cccgccatgg tctaaactga cgtattccaa accgcatgac
5460gcggcgacgt tttactgtcc ttttctctat ccctcgcccc cacggtcccc cttgcaattc
5520tcggggttcc agcaggtatc aacgggtccc gagtgtcgca acgagaccct gtatctgctg
5580tacaaccggg aaggccagac cttggtggag agaagctcca cctgggtgaa aaaggtgatc
5640tggtatctga gcggtcgcaa ccagaccatc ctccaacgga tgccccaaac ggcttcgaaa
5700ccgagcgacg gaaacgtgca gatcagcgtg gaagacgcca agatttttgg agcgcacatg
5760gtgcccaagc agaccaagct gctacgcttc gtcgtcaacg atggcacgcg ttatcagatg
5820tgtgtgatga agctggagag ctgggcccac gtcttccggg actacagcgt gtcttttcag
5880gtgcgattga cgttcaccga ggccaataac cagacttaca ccttctgtac ccatcccaat
5940ctcatcattt gagcccgtcg cgcgcgcagg gaattttgaa aaccgcgcgt catgagtccc
6000aaagacctga cgccgttctt gacgacgttg tggctgctat tgggtcacag ccgcgtgccg
6060cgggtgcgcg cagaagaatg ttgcgaattc ataaacgtca accacccgcc ggaacgctgt
6120tacgatttca aaatgtgcaa tcgcttcacc gtcgcgtacg tattttcatg attgtctgcg
6180ttctgtggtg cgtctggatt tgtctctcga cgtttctgat agccatgttc catcgacgat
6240cctcgggaat gccagagtag attttcatga atccacaggc tgcggtgtcc ggacggcgaa
6300gtctgctaca gtcccgagaa aacggctgag attcgcggga tcgtcaccac catgacccat
6360tcattgacac gccaggtcgt acacaacaaa ctgacgagct gcaactacaa tccgtaagtc
6420tcttcctcga gggccttaca gcctatggga gagtaagaca gagagggaca aaacatcatt
6480aaaaaaaaaa gtctaatttc acgttttgta ccccccttcc cctccgtgtt gtagcccatc
6540ggccgcggcg atctcctagt aacactcgtc cgacacttcc accatctcca gctcggccgg
6600cggttcggca tcctctacca gcggcgtcgt ctcatctttg ccgcagcagc ggacgcacac
6660cttctccagg cagaacgcca ccagctgccg ccgaacgtac cacaggtaca cgtgcagacc
6720tgcgaacagg actacggagg tcatgaccac cacgacgcac acgggaatcc agggatcgag
6780attgttgctg gaactcgcta tcgccaccga cgtgcccgcg tctgtctcac cgccgctcgc
6840ccgatgtcgc gcggcttgtt atacgctagc ccgtcgccgc ctcggggcac ggtgccctcc
6900tacccacgta acttcctccg tgacttaaag tcgcgtgtgg tagatctcct gctccgtgga
6960cgaaccgtcc ggcaggatag cggttaagga ttcggtgcta aggccgtgtc gccaacgtcg
7020aatgctacgt tgcaacagct tcgacggacg gccatcccct ctctcatcgc aataataaaa
7080caccagcagc gcgcacgacg cgatcacggt gacacccatg attagaccca cgcagatagc
7140cagccccgct agcgtatcta gcgccatccc gttcgctccc gttgtctcct gagcgaagca
7200acttctcggt ccccgttttc aacagttttt gtttccttct ccgcgactag atgttaacgc
7260ccgcggtctt tccggccgtg ctctacctcc tggcgcttgt cgtctgggtt gagatgttct
7320gcctcgtcgc cgtagccgtc gtcgagcgcg agatcgcctg ggcgctgctg ctgcggatgc
7380tggtcgttgg cctgatggtg gaagtcggcg ccgccgccgc ttggaccttc gtgcgttgtc
7440ttgcctatca gcgctccttc cccgtgctta cggccttccc ctgaaaccca cgttaaccga
7500ccgtcccaaa aacgccggtg ttaacacagg aaaaaaagaa accacgcagg aaccgcgcag
7560gaaccacgcg gaacatggga cactatctgg aaatcctgtt caacgtcatc gtcttcactc
7620tgctgctcgg cgtcatggtc agtatcgtcg
7650576136DNAHuman cytomegalovirus 57tttaaacctc tgtgttgtgt gattgattgg
tatgtggggg gatccgattt caaagggggg 60tacttatcgg gaattgatgt gtcatggacg
cagttttgag cgattttccg ggaataccgg 120atattacgaa ttactggtag tgacgtagat
aataaaatta taatgcgatt aatttttggt 180gcgttgatta tttttttagc atatgtgtat
cattatgagg tgaatggaac agaattacgc 240tgcagatgtc ttcatagaaa atggccgcct
aataaaatta tattgggtaa ttattggctt 300catcgcgatc ccagagggcc cggatgcgat
aaaaatgaac atttattgta tccagacgga 360aggaaaccgc ctggacctgg agtatgttta
tcgcccgatc acctcttctc aaaatggtta 420gacaaacaca acgataatag gtggtataat
gttaacataa cgaaatcacc aggaccgaga 480cgaataaata taaccttgat aggtgttaga
ggataatatt taatgtatgt tttcaaacag 540acaagttcgt taaaacaaaa tattacagta
tgtgtttaat atggtgctaa catggttgca 600ccatccggtt tcaaactcgc atatcaatct
gttatcggta cgacacctgt cattaatcgc 660atatatgtta cttaccatat gtcccctagc
cgtccatgtt ttagaactag aagattacga 720caggcgctgc cgttgcaaca accaaattct
gttgaatacc ctgccggtcg gaaccgaatt 780gcttaagcca atcgcagcga gcgaaagctg
caatcgtcag gaagtgctgg ctattttaaa 840ggacaaggga accaagtgtc tcaatcctaa
cgcgcaagcc gtgcgtcgtc acatcaaccg 900gctatttttt cggttaatct tagacgagga
acaacgcatt tacgacgtag tgtctaccaa 960tattgagttc ggtgcctggc cagtccctac
ggcctacaaa gcctttcttt ggaaatacgc 1020caagagactg aactaccacc acttcagact
gcgctggtga tcatgtccct attttaccgt 1080gcggtagctc tgggcacgct aagcgctttg
gtgtggtaca gcactagcat cctcgcagag 1140attaacgaaa attcctgctc ctcatcttct
gcggatcacg aagactgcga ggaaccggac 1200gagatcgttc gcgaagagca agactatcgg
gctctgctgg ccttttccct agtgatttgc 1260ggtacgctcc tcgtcacttg tgtgatctga
gacgtcatgc tggtagcgtt tatgagtcgg 1320gcggtggccg acacgccgca tttcctaacc
cgcgcagcat gttgcgcttg ctgttcacgc 1380tcgtcctgct ggccctccac gggcagtctg
tcggcgctag ccgcgactat gtgcatgttc 1440ggctactgag ctaccgaggc gaccccctgg
tcttcaagca cactttctcg ggtgtgcgtc 1500gacccttcac cgagctaggc tgggctgcgt
gtcgcgactg ggacagtatg cattgcacac 1560ccttctggtc taccgatctg gagcagatga
ccgactcggt gcggcgttac agcacggtga 1620gccccggcaa ggaagtgacg cttcagcttc
acgggaacca aaccgtacag ccgtcgtttc 1680taagctttac gtgccgcctg cagctagaac
ccgtggtgga aaatgttggc ctctacgtgg 1740cctacgtggt caacgacggc gaacgcccac
aacagttttt tacaccgcag gtagacgtgg 1800tacgctttgc tctatatcta gaaacactct
cccggatcgt ggaaccgtta gaatcaggtc 1860gcctggcagt ggaatttgat acgcctgacc
tagctctggc gcccgattta gtaagcagcc 1920tcttcgtggc cggacacggc gagaccgact
tttacatgaa ctggacgctg cgtcgcagtc 1980agacccacta cctggaggag atggccttac
aggtggagat tctaaaaccc cgcggcgtac 2040gtcaccgcgc tattatccac catccgaagc
tacagccggg cgttggcctg tggatagatt 2100tctgcgtgta ccgctacaac gcgcgcctga
cccgcggcta cgtacgatac accctgtcac 2160cgaaagcgcg cttgcccgca aaagcagagg
gttggctggt gtcactagac agattcatcg 2220tgcagtacct caacacattg ctgattacaa
tgatggcggc gatatgggct cgcgttttga 2280taacctacct ggtgtcgcgg cgtcggtaga
ggcttgcgga aaccacgtcc tcgtcacacg 2340tcgttcgcgg acatagcaag aaatccacgt
cgccacatct cgagaatgcc ggccttgcgg 2400ggtccccttc gcgcaacatt cctggccctg
gtcgcgttcg ggttgctgct tcagatagac 2460ctcagcgacg ctacgaatgt gaccagcagc
acaaaagtcc ctactagcac cagcaacaga 2520aataacgtcg acaacgccac gagtagcgga
cccacaaccg ggatcaacat gaccaccacc 2580cacgagtctt ccgttcacaa cgtgcgcaat
aacgagatca tgaaagtgct ggctatcctc 2640ttctacatcg tgacaggcac ctccattttc
agcttcatag cggtactgat cgcggtagtt 2700tactcctcgt gttgcaagca cccgggccgc
tttcgtttcg ccgacgaaga ggccgtcaac 2760ctgttggacg acacggacga cagtggcggc
agcagcccgt ttggcagcgg ttcccgacga 2820ggttctcaga tccccgccgg attttgttcc
tcgagccctt atcagcggtt ggaaactcgg 2880gactgggacg aggaggagga ggcgtccgcg
gcccgcgagc gcatgaaaca tgatcctgag 2940aacgtcatct atttcagaaa ggatggcaac
ttggacacgt cgttcgtgaa tcccaattat 3000gggagaggct cgcctttgac catcgaatct
cacctctcgg acaatgagga ggaccccatc 3060aggtactacg tttcggtgta cgatgaactg
accgcctcgg aaatggaaga accttcgaac 3120agcaccagct ggcagattcc caaactaatg
aaagttgcca tgcaacccgt ctcgctcaga 3180gatcccgagt acgactaggc tttttttttt
gtctttcggt tccaactctt tccccgcccc 3240atcacctcgc ctgtactatg tgtatgatgt
ctcataataa agctttcttt ctcagtctgc 3300aacatgcagc tgtgtcgggt gtggctgtct
gtttgtctgt gcgccgtggt gctgggtcag 3360tgccagcggg aaaccgcgga aaaaaacgat
tattaccgag taccgcatta ctgggacgcg 3420tgctctcgcg cgctgcccga ccaaacccgt
tacaagtatg tggaacagct cgtggacctc 3480acgttgaact accactacga tgcgagccac
ggcttggaca actttgacgt gctcaagagg 3540tgagggtacg cgctaaaggt gcatgacaac
gggaaggtaa gggcgaacgg gtaacggcta 3600agtaaccgca tggggtatga aatgacgttt
ggaacctgtg cttgcagaat caacgtgacc 3660gaggtgtcgt tgctcatcag cgactttaga
cgtcagaacc gtcgcggcgg caccaacaaa 3720aggaccacgt tcaacgccgc cggttcgctg
gcgccacacg cccggagcct cgagttcagc 3780gtgcggctct ttgccaacta gcctgcgtca
cgggaaataa tatgctgcgg cttctgcttc 3840gtcaccactt tcactgcctg cttctgtgcg
cggtttgggc aacgccctgt ctggcgtctc 3900cgtggtcgac gctaacggca aaccagaatc
cgtccccgcc atggtctaaa ctgacgtatt 3960ccaaaccgca tgacgcggcg acgttttact
gtccttttct ctatccctcg cccccacggt 4020cccccttgca attctcgggg ttccagcagg
tatcaacggg tcccgagtgt cgcaacgaga 4080ccctgtatct gctgtacaac cgggaaggcc
agaccttggt ggagagaagc tccacctggg 4140tgaaaaaggt gatctggtat ctgagcggtc
gcaaccagac catcctccaa cggatgcccc 4200aaacggcttc gaaaccgagc gacggaaacg
tgcagatcag cgtggaagac gccaagattt 4260ttggagcgca catggtgccc aagcagacca
agctgctacg cttcgtcgtc aacgatggca 4320cgcgttatca gatgtgtgtg atgaagctgg
agagctgggc ccacgtcttc cgggactaca 4380gcgtgtcttt tcaggtgcga ttgacgttca
ccgaggccaa taaccagact tacaccttct 4440gtacccatcc caatctcatc atttgagccc
gtcgcgcgcg cagggaattt tgaaaaccgc 4500gcgtcatgag tcccaaagac ctgacgccgt
tcttgacgac gttgtggctg ctattgggtc 4560acagccgcgt gccgcgggtg cgcgcagaag
aatgttgcga attcataaac gtcaaccacc 4620cgccggaacg ctgttacgat ttcaaaatgt
gcaatcgctt caccgtcgcg tacgtatttt 4680catgattgtc tgcgttctgt ggtgcgtctg
gatttgtctc tcgacgtttc tgatagccat 4740gttccatcga cgatcctcgg gaatgccaga
gtagattttc atgaatccac aggctgcggt 4800gtccggacgg cgaagtctgc tacagtcccg
agaaaacggc tgagattcgc gggatcgtca 4860ccaccatgac ccattcattg acacgccagg
tcgtacacaa caaactgacg agctgcaact 4920acaatccgta agtctcttcc tcgagggcct
tacagcctat gggagagtaa gacagagagg 4980gacaaaacat cattaaaaaa aaaagtctaa
tttcacgttt tgtacccccc ttcccctccg 5040tgttgtagcc catcggccgc ggcgatctcc
tagtaacact cgtccgacac ttccaccatc 5100tccagctcgg ccggcggttc ggcatcctct
accagcggcg tcgtctcatc tttgccgcag 5160cagcggacgc acaccttctc caggcagaac
gccaccagct gccgccgaac gtaccacagg 5220tacacgtgca gacctgcgaa caggactacg
gaggtcatga ccaccacgac gcacacggga 5280atccagggat cgagattgtt gctggaactc
gctatcgcca ccgacgtgcc cgcgtctgtc 5340tcaccgccgc tcgcccgatg tcgcgcggct
tgttatacgc tagcccgtcg ccgcctcggg 5400gcacggtgcc ctcctaccca cgtaacttcc
tccgtgactt aaagtcgcgt gtggtagatc 5460tcctgctccg tggacgaacc gtccggcagg
atagcggtta aggattcggt gctaaggccg 5520tgtcgccaac gtcgaatgct acgttgcaac
agcttcgacg gacggccatc ccctctctca 5580tcgcaataat aaaacaccag cagcgcgcac
gacgcgatca cggtgacacc catgattaga 5640cccacgcaga tagccagccc cgctagcgta
tctagcgcca tcccgttcgc tcccgttgtc 5700tcctgagcga agcaacttct cggtccccgt
tttcaacagt ttttgtttcc ttctccgcga 5760ctagatgtta acgcccgcgg tctttccggc
cgtgctctac ctcctggcgc ttgtcgtctg 5820ggttgagatg ttctgcctcg tcgccgtagc
cgtcgtcgag cgcgagatcg cctgggcgct 5880gctgctgcgg atgctggtcg ttggcctgat
ggtggaagtc ggcgccgccg ccgcttggac 5940cttcgtgcgt tgtcttgcct atcagcgctc
cttccccgtg cttacggcct tcccctgaaa 6000cccacgttaa ccgaccgtcc caaaaacgcc
ggtgttaaca caggaaaaaa agaaaccacg 6060caggaaccgc gcaggaacca cgcggaacat
gggacactat ctggaaatcc tgttcaacgt 6120catcgtcttc actctg
61365815549DNAHuman cytomegalovirus
58cgctgtaggg ataaatagtg cgatggcgtt tgtgggagaa cgcagtagcg atgggttgcg
60acgtgcacga tccttcgtgg caatgccaat ggggcgttcc cacgattatc gtggcctgga
120taacatgcgc ggctttagga atttggtgtt tggcgggatc gtcggcggat gtctcttcgg
180gacccggcat cgcagccgta gtcggctgtt ctgttttcat gattttcctc tgcgcgtatc
240tcatccgtta ccgggaattc ttcaaagact ccgtaatcga cctccttacc tgccgatggg
300ttcgctactg cagctgcagc tgtaagtgca gctgcaaatg catctcgggc ccctgtagcc
360gctgctgttc agcgtgttac aaggagacga tgatttacga catggtccaa tacggtcatc
420gacggcgtcc cggacacggc gacgatcccg acagggtgat ctgcgagata gtcgagagtc
480ccccggtttc ggcgccgacg gtgtccgtcc ccccgccgtc ggaggagtcc caccagcccg
540tcatcccacc gcagccgcca gcaccgacat cggaacccaa accgaagaaa ggtagggcga
600aagataaacc gaagggtaga ccgaaagaca aacctccgtg cgaaccgacg gtgagttcac
660aaccaccgtc gcagccgacg gcaatgcccg gcggtccgcc cgacgcgcct ccccccgcca
720tgccgcagat gccacccggc gtggccgagg cggtacaagc tgccgtgcag gcggccgtgg
780ccgcggctct acaacaacag cagcagcatc agaccggaac gtaacccgcc cccggtgcga
840taaggaattt tccgacttgg cgcacatctc cttcctcaat gtttggacaa taaacacatt
900ccttgccaaa aaatgacgtt tccagaaatc caaggcataa atgtccgtac accggccctt
960cccaacacgg agtttgagat tccaagcagg agagaagatc atggtgtgga tatggctcgg
1020catcgggctc ctcggcggta ccggactggc ttccctggtc ctggccattt ccttatttac
1080ccagcgccga ggccgcaagc gatccgacga gacttcgtcg cgaggccggc tcccgggtgc
1140tgcttctgat aagcgtggtg cctgcgcgtg ctgctatcga aatccgaaag aagacgtcgt
1200cgagccgctg gatctggaac tggggctcat gcgggtggac acccacccgc cgacgccgca
1260ggtgccgcgg tgtacgtcgc tctacatagg agaggatggt ctgccgatag ataaacccga
1320gtttcctccg gcgcggttcg agatccccga cgtatccacg ccgggaacgc cgaccagcat
1380cggccgatct ccgtcgcatt gctcctcgtc gagctctttg tcgtcctcga ccagcgtcga
1440cacggtgctg tatcagccgc cgccatcctg gaagccacct ccgccgcccg ggcgcaagaa
1500gcggccgcct acgccgccgg tccgggcccc caccacgcgg ctgtcgtcgc acagaccccc
1560gacgccgata cccgcgccgc gtaagaacct gagcacgccg cccaccaaga aaacgccgcc
1620gcccacgaaa cccaagccgg tcggctggac accgccggtg acacccaggc ccttcccgaa
1680aacgccgacg ccacaaaagc cgccgcggaa tccgagacta ccgcgcaccg tcggtctgga
1740gaatctctcg aaggtgggac tctcgtgtcc ctgtccccga ccccgcacgc cgacggagcc
1800gaccacgctg cctatcgtgt cggtttccga gctagccccg cctcctcgat ggtcggacat
1860cgaggaactc ttggaacagg cggtgcagag cgtcatgaag gacgccgagt cgatgcagat
1920gacctgagac cgaaagagcg agcgcgtccg ttgtacagtt gtatagcagc acacgccttc
1980cctctttttc accgcagcta agagagagaa agagagtatg tcagtcaagg gcgtggagat
2040gccagaaatg acgtgggact tggacgttag aaataaatgg cggcgtcgaa aggccctgag
2100tcgcattcac cggttctggg aatgtcggct acgggtgtgg tggctgagtg acgccggcgt
2160aagagaaacc gacccaccgc gtccccgacg ccgcccgact tggatgaccg cggtgtttca
2220cgttatctgt gccgttttgc ttacgcttat gattatggcc atcggcgcgc tcatcgcgta
2280cttaagatat taccaccagg acagttggcg agacatgctc cacgatctat tttgcggctg
2340tcattatccc gagaagtgcc gtcggcacca cgagcggcag agaaggagac ggcaagccat
2400ggatgtgccc gacccggaac tcggcgaccc ggcccgccgg ccgttgaacg gagctatgta
2460ctacggcagc ggctgtcgct tcgacacggt ggaaatggtg gacgagacga gacccgcgcc
2520gccggcgctg tcatcgcccg aaaccggcga cgatagcaac gacgacgcgg ttgccggcgg
2580aggtgctggc ggggtaacat cacccgcgac tcgtacgacg tcgccgaacg cactgctgcc
2640agaatggatg gatgcggtgc atgtggcggt ccaagccgcc gttcaagcga ccgtgcaagt
2700aagtggcccg cgggagaacg ccgtatctcc cgctacgtaa gagggttgag ggggccgttc
2760ccgcgcgagt gctgtacaaa agagagagac tgggacgtag atccggacag aggacggtca
2820ccatggacga tctgccgctg aatgtcgggt tacccatcat cggcgtgatg ctcgtgctga
2880tcgtggccat cctctgctat ctggcttacc actggcacga caccttcaaa ctggtgcgca
2940tgtttctgag ctaccgctgg ctgatccgct gttgcgagct gtacggggag tacgagcgcc
3000ggttcgcgga cctgtcgtct ctgggcctcg gcgccgtacg gcgggagtcg gacagacgat
3060accgtttctc cgaacggccc gacgagatct tggtccgttg ggaggaagtg tcttcccagt
3120gcagctacgc gtcgtcgcgg ataacagacc gccgtgtggg ttcatcgtct tcgtcgtcgg
3180tccacgtcgc tagccagaga aacagcgtgc ctccgccgga catggcggtg acggcgccgc
3240tgaccgacgt cgatctgttg aaacccgtga cgggatccgc gacgcagttc accaccgtag
3300ccatggtaca ttatcatcaa gagtacacgt gaatgagaaa aagaaaaaag aggggagcgg
3360atcgcgataa tgtcgctttg acattctctg ctcgatctac tcagcgtctg cacgaaacgg
3420catccgcacg gaggcgagcc caagcgtatc tgcagcaagc ggttctttcc ctcggtgatg
3480gtggcagcat cggtggcggg agcttgttcg gacgatggac ggtgaggagt ccctggcgat
3540caggcggctc ccgggtgtgg agttcaacgg gtggtaatgg tggcggtgat cggtgttaga
3600aaacggtggc cctggcaaac atatatctac tgtaaaccct ctgctctgtt aataaaaagc
3660acacttttca catgagttcg taattttatt gtgtagtgga aatttttacg tcattgggaa
3720accccagaat gaaagagtat aatgtgcata tcaccggggg ttccctgtca gtacgaatgt
3780acacaacgcg ggttacatta cgataaactt tccggtaaaa cgatgccgat acagcgtgta
3840taacgctgat tgttacgaca aacgagttgg tatatccatt atatagtaac gaacatgctg
3900tggatattag ttttatttgc actcgccgca tcggcgagtg aaaccactac aggtaccagc
3960tctaattcca gtcaatctac tagtgctacc gccaacacga ccgtatcgac atgtattaat
4020gcctctaacg gcagtagctg gacagtacca cagctcgcgc tgcttgccgc tagcggctgg
4080acattatctg gactccttct cttatttacc tgctgctttt gctgcttttg gctagtacgt
4140aaaatctgca gctgctgcgg caactcctcc gagtcagaga gcaaaacaac ccacgcgtac
4200accaatgccg cattcacttc ttccgacgca acgttaccca tgggcactac agggtcgtac
4260actcccccac aggacggctc atttccacct ccgcctcggt gacgtaggct aaaccgaaac
4320ccacgttgaa cctaacgcgg tttcggaagg cctgagacgt cactttcaca atgacgtccg
4380tatacacgtt catcataaaa caccgtagag gctaaggctt cggtagggag agacctcaac
4440tgttcctgat gagcacccgt gctctcatct cttcagactt gtcatgaccc ccgctcagac
4500taacgcgact accaccgtgc acccgcacga cgcaaaaaac ggcagcggcg gtagtgccct
4560gccgaccctc gtcgttttcg gctttatcgt tacgctactt ttctttctct ttatgctcta
4620cttttggaac aacgacgtgt tccgtaagct gctccgtgcg cttggatcca gcgctgttgc
4680gaccgcttcg acgcgtggca agacgaggtc atctaccgtc gtccatcacg tcgttcccag
4740agcgacgacg agagtcgtac taacagcgtg tcatcgtacg ttcttttatc acccgcgtcc
4800gatggcggtt ttgacaaccc ggcactgaca gaggccgtcg acagcgtgga cgactgggcg
4860accacctcgg ttttctacgc cacgtccgac gaaacggcgg acgccgagcg ccgagactcg
4920cagcaactgc tcatcgagct tccgccggag ccgctcccgc ccgacgtggt ggcggccatg
4980cagaaagcag tgaaacgcgc tgtacagaac gcactacgac acagccacga ctcttggcag
5040cttcatcaga ccctgtgacg ccagatgaac gttccttctt aaacatccga ggtagcaatg
5100agacaggtcg cgtaccgccg gcgacgcgag agttcctgcg cggtgctggt ccaccacgtc
5160ggccgcgacg gcgacggcga gggggaggca gcaaaaaaga cctgcaaaaa aaccggacgc
5220tcagttgcgg gcatcccggg cgagaagctg cgtcgcacgg tggtcaccac cacgccggcc
5280cgacgtttga gcggccgaca cacggagcag gagcaggcgg gcatgcgtct ctgtgaaaaa
5340gggaagaaaa gaatcatcat gtgccgccgg gagtcgctcc gaactctgcc gtggctgttc
5400tgggtgctgt tgagctgccc gcgactcctc gaatattctt cctcttcgtt ccccttcgcc
5460accgctgaca ttgccgaaaa gatgtgggcc gagaattatg agaccacgtc gccggcgccg
5520gtgttggtcg ccgagggaga gcaagttacc atcccctgca cggtcatgac acactcctgg
5580cccatggtct ccattcgcgc acgtttctgt cgttcccacg acggcagcga cgagctcatc
5640ctggacgccg tcaaaggcca tcggctgatg aacggactcc agtaccgcct gccgtacgcc
5700acttggaatt tctcgcaatt gcatctcggc caaatattct cgcttacttt taacgtatcg
5760atggacacag ccggcatgta cgaatgcgtg ctacgcaact acagccacgg cctcatcatg
5820caacgcttcg taattctcac gcagctggag acgctcagcc ggcccgacga accttgctgc
5880acaccggcgt taggtcgcta ctcgctggga gaccagatct ggtcgccgac gccctggcgt
5940ctacggaatc acgactgcgg aacgtaccgc ggctttcaac gcaactactt ctatatcggc
6000cgcgccgacg ccgaggattg ctggaaaccc gcatgtccgg acgaggaacc cgaccgctgt
6060tggacagtga tacagcgtta ccggctcccc ggcgactgct accgttcgca gccacacccg
6120ccgaaatttt taccggtgac gccagcaccg ccggccgaca tagacaccgg gatgtctccc
6180tgggccactc ggggaatcgc ggcgtttttg gggttttgga gtatttttac cgtatgtttc
6240ctatgctacc tgtgttatct gcagtgttgt ggacgctggt gtcccacgcc gggaagggga
6300cgacgaggcg gtgagggcta tcgacgccta ccgacttacg atagttaccc cggtgttaga
6360aagatgaaga ggtgagaaca cgtataaaat aaaaaaataa tatgttaaaa aatgcagtgt
6420gtgaagtgtg aatagtgtga ttaaaatatg cggattgaat gggtgtggtg gttattcgga
6480tactttgtgt catccgttgg gagcgaacgg tcattatcct atcgttacca cttggaatct
6540aattcatcta ccaacgtggt ttgcaacgga aacatttccg tgtttgtaaa cggcacccta
6600ggtgtgcggt ataacattac ggtaggaatc agttcgtctt tattaatagg acaccttact
6660atacaagtat tggaatcatg gttcacaccc tgggtccaaa ataaaagtta caacaaacaa
6720cccctaggtg acactgaaac gctttataat atagatagcg aaaacattca tcgcgtatct
6780caatattttc acacaagatg gataaaatct ctgcaagaga atcacacttg cgacctcaca
6840aacagtacac ctacctatac atatcaagta aacgtgaaca acacgaatta cctaacacta
6900acatcctcgg gatggcaaga ccgtctaaat tacaccgtca taaatagtac acactttaac
6960ctcacagaat cgaacataac cagcattcaa aaatatctca acactacctg catagaaaga
7020ctccgtaact acaccttgga gtccgtatac accacaactg tgcctcaaaa cataacaaca
7080tctcaacacg caacaaccac tatgcacaca atacctccaa atacaataac aattcaaaat
7140acaactcaaa gccatactgt acagacgccg tcttttaacg acacacataa cgtgacgaaa
7200cacacgttaa acataagcta cgttttatca caaaaaacga ataacacaac atcaccgtgg
7260atatatgcca tacctatggg cgctacagcc acaataggcg ccggtttata tatcgggaaa
7320cactttacgc cggttaagtt cgtatacgag gtatggcgcg gtcagtaaag acgattcgga
7380ttcaacacat atactcccca cgatcctcga acaccttaca gcatatgagc aaaaaacaag
7440aaagtatagc cacaatcaca tttgggcgaa taacatgctg tcatccacta gcgtctatta
7500atctaatgtt taacgggagc tgtactgtca ccgttaaaat atccatggga atcaacgggt
7560caaccaacgt ccatcagctt gtgattgtgc tccatctggg taaccgctgt cagccttggc
7620gacaggtgta atcacagctg tcacataact cacgaagcct ccaatcacag cagcacacat
7680agtcctaacg ccattggcgt gtataaaagt tcggaaaact tgacggttgt acggcacgac
7740aaatcgatgt agtggtatgt ttttccagca gagaccgtgt gcggtctctt aggttcgcta
7800tactgtggct ggaaactggt tacctgtgaa gatggctaac tatcctgttc tgtcctggaa
7860aaacttttgg cgtcgtaggt ggactttgca gtatgcgggt tagtgaagtt atgtcattta
7920tttacgttta cgatctcgta ttacaaaccg cggagaggat gataccgttc ggccccatga
7980gttattttta ttcttccggt aggaggcatg aagcctctga taatgctcat ctgctttgct
8040gtgatattat tgcagcttgg agtgactaaa gtgtgtcagc ataatgaagt gcaactgggc
8100aatgagtgct gccctccgtg tggttcggga caaagagtta ctaaagtatg cacggattat
8160accagtgtaa cgtgtacccc ttgccccaac ggcacgtatg tatcgggact ttacaactgt
8220accgattgca ctcaatgtaa cgtcactcag gtcatgattc gtaactgcac ttccaccaat
8280aataccgtat gcgcacctaa gaaccatacg tacttttcca ctccaggcgt ccaacatcac
8340aaacaacgac agcaaaatca taccgcacat ataaccgtca aacaaggaaa aagcggtcgt
8400catactctag cctggttgtc tctctttatc tttcttgtgg gtatcatact tttaattctc
8460tatcttatag ccgcctatcg gagtgagaga tgccaacagt gttgctcaat cggcaaaatt
8520ttctaccgca ccctgtaagc ttcctgttgt tgtttttaca tcacggtacg atgaagtcac
8580acagataatt acagatgagc tgttcatatt ttttattatt ttttccaatt cctgcactaa
8640aaaaagaagc actttacgga accgtgtctg agtatctgtg gggaatttag gtactttttg
8700ccgacgtcag gaaaaataag tgtcgcctac ataagagccc ggtgctatcg tgctgtcact
8760ctttcttgtt gccttcgatg tacggcgtcc tggctcatta ctactccttc atcagtagcc
8820ccagcgttat ggttaatttt aagcatcata acgccgtgca gctgttatgt gcacggaccc
8880gagacgcact gccggatggg aacgtttaac ccatcatgcg tcgtatcacg cgaactacgg
8940ggcatacgcc gtgttgatgg ctacatcgca aagaaagtcc ctagtgttac atcgatacag
9000tgccgtgaca gccgtggccc tgcagctcat gcctgttgag atcgtccgca agctagatca
9060gtcggactgg gtgcggggtg cctggatcgt gtcagagact tttccaacta gcgaccccaa
9120aggagtttgg agcgacgatg actcctcgat gggtggaagt gatgattgat gatgagaacc
9180tgacaagaaa gacgagagag aaatttagag ctgtcattgt agaattagtc tagattcctg
9240ataataaaca gtatcgattt tgaaacctaa ttgacgtgtg atcgattttt aaacctctgt
9300gttgtgtgat tgattggtat gtggggggat ccgatttcaa aggggggtac ttatcgggaa
9360ttgatgtgtc atggacgcag ttttgagcga ttttccggga ataccggata ttacgaatta
9420ctggtagtga cgtagataat aaaattataa tgcgattaat ttttggtgcg ttgattattt
9480ttttagcata tgtgtatcat tatgaggtga atggaacaga attacgctgc agatgtcttc
9540atagaaaatg gccgcctaat aaaattatat tgggtaatta ttggcttcat cgcgatccca
9600gagggcccgg atgcgataaa aatgaacatt tattgtatcc agacggaagg aaaccgcctg
9660gacctggagt atgtttatcg cccgatcacc tcttctcaaa atggttagac aaacacaacg
9720ataataggtg gtataatgtt aacataacga aatcaccagg accgagacga ataaatataa
9780ccttgatagg tgttagagga taatatttaa tgtatgtttt caaacagaca agttcgttaa
9840aacaaaatat tacagtatgt gtttaatatg gtgctaacat ggttgcacca tccggtttca
9900aactcgcata tcaatctgtt atcggtacga cacctgtcat taatcgcata tatgttactt
9960accatatgtc ccctagccgt ccatgtttta gaactagaag attacgacag gcgctgccgt
10020tgcaacaacc aaattctgtt gaataccctg ccggtcggaa ccgaattgct taagccaatc
10080gcagcgagcg aaagctgcaa tcgtcaggaa gtgctggcta ttttaaagga caagggaacc
10140aagtgtctca atcctaacgc gcaagccgtg cgtcgtcaca tcaaccggct attttttcgg
10200ttaatcttag acgaggaaca acgcatttac gacgtagtgt ctaccaatat tgagttcggt
10260gcctggccag tccctacggc ctacaaagcc tttctttgga aatacgccaa gagactgaac
10320taccaccact tcagactgcg ctggtgatca tgtccctatt ttaccgtgcg gtagctctgg
10380gcacgctaag cgctttggtg tggtacagca ctagcatcct cgcagagatt aacgaaaatt
10440cctgctcctc atcttctgcg gatcacgaag actgcgagga accggacgag atcgttcgcg
10500aagagcaaga ctatcgggct ctgctggcct tttccctagt gatttgcggt acgctcctcg
10560tcacttgtgt gatctgagac gtcatgctgg tagcgtttat gagtcgggcg gtggccgaca
10620cgccgcattt cctaacccgc gcagcatgtt gcgcttgctg ttcacgctcg tcctgctggc
10680cctccacggg cagtctgtcg gcgctagccg cgactatgtg catgttcggc tactgagcta
10740ccgaggcgac cccctggtct tcaagcacac tttctcgggt gtgcgtcgac ccttcaccga
10800gctaggctgg gctgcgtgtc gcgactggga cagtatgcat tgcacaccct tctggtctac
10860cgatctggag cagatgaccg actcggtgcg gcgttacagc acggtgagcc ccggcaagga
10920agtgacgctt cagcttcacg ggaaccaaac cgtacagccg tcgtttctaa gctttacgtg
10980ccgcctgcag ctagaacccg tggtggaaaa tgttggcctc tacgtggcct acgtggtcaa
11040cgacggcgaa cgcccacaac agttttttac accgcaggta gacgtggtac gctttgctct
11100atatctagaa acactctccc ggatcgtgga accgttagaa tcaggtcgcc tggcagtgga
11160atttgatacg cctgacctag ctctggcgcc cgatttagta agcagcctct tcgtggccgg
11220acacggcgag accgactttt acatgaactg gacgctgcgt cgcagtcaga cccactacct
11280ggaggagatg gccttacagg tggagattct aaaaccccgc ggcgtacgtc accgcgctat
11340tatccaccat ccgaagctac agccgggcgt tggcctgtgg atagatttct gcgtgtaccg
11400ctacaacgcg cgcctgaccc gcggctacgt acgatacacc ctgtcaccga aagcgcgctt
11460gcccgcaaaa gcagagggtt ggctggtgtc actagacaga ttcatcgtgc agtacctcaa
11520cacattgctg attacaatga tggcggcgat atgggctcgc gttttgataa cctacctggt
11580gtcgcggcgt cggtagaggc ttgcggaaac cacgtcctcg tcacacgtcg ttcgcggaca
11640tagcaagaaa tccacgtcgc cacatctcga gaatgccggc cttgcggggt ccccttcgcg
11700caacattcct ggccctggtc gcgttcgggt tgctgcttca gatagacctc agcgacgcta
11760cgaatgtgac cagcagcaca aaagtcccta ctagcaccag caacagaaat aacgtcgaca
11820acgccacgag tagcggaccc acaaccggga tcaacatgac caccacccac gagtcttccg
11880ttcacaacgt gcgcaataac gagatcatga aagtgctggc tatcctcttc tacatcgtga
11940caggcacctc cattttcagc ttcatagcgg tactgatcgc ggtagtttac tcctcgtgtt
12000gcaagcaccc gggccgcttt cgtttcgccg acgaagaggc cgtcaacctg ttggacgaca
12060cggacgacag tggcggcagc agcccgtttg gcagcggttc ccgacgaggt tctcagatcc
12120ccgccggatt ttgttcctcg agcccttatc agcggttgga aactcgggac tgggacgagg
12180aggaggaggc gtccgcggcc cgcgagcgca tgaaacatga tcctgagaac gtcatctatt
12240tcagaaagga tggcaacttg gacacgtcgt tcgtgaatcc caattatggg agaggctcgc
12300ctttgaccat cgaatctcac ctctcggaca atgaggagga ccccatcagg tactacgttt
12360cggtgtacga tgaactgacc gcctcggaaa tggaagaacc ttcgaacagc accagctggc
12420agattcccaa actaatgaaa gttgccatgc aacccgtctc gctcagagat cccgagtacg
12480actaggcttt tttttttgtc tttcggttcc aactctttcc ccgccccatc acctcgcctg
12540tactatgtgt atgatgtctc ataataaagc tttctttctc agtctgcaac atgcagctgt
12600gtcgggtgtg gctgtctgtt tgtctgtgcg ccgtggtgct gggtcagtgc cagcgggaaa
12660ccgcggaaaa aaacgattat taccgagtac cgcattactg ggacgcgtgc tctcgcgcgc
12720tgcccgacca aacccgttac aagtatgtgg aacagctcgt ggacctcacg ttgaactacc
12780actacgatgc gagccacggc ttggacaact ttgacgtgct caagaggtga gggtacgcgc
12840taaaggtgca tgacaacggg aaggtaaggg cgaacgggta acggctaagt aaccgcatgg
12900ggtatgaaat gacgtttgga acctgtgctt gcagaatcaa cgtgaccgag gtgtcgttgc
12960tcatcagcga ctttagacgt cagaaccgtc gcggcggcac caacaaaagg accacgttca
13020acgccgccgg ttcgctggcg ccacacgccc ggagcctcga gttcagcgtg cggctctttg
13080ccaactagcc tgcgtcacgg gaaataatat gctgcggctt ctgcttcgtc accactttca
13140ctgcctgctt ctgtgcgcgg tttgggcaac gccctgtctg gcgtctccgt ggtcgacgct
13200aacggcaaac cagaatccgt ccccgccatg gtctaaactg acgtattcca aaccgcatga
13260cgcggcgacg ttttactgtc cttttctcta tccctcgccc ccacggtccc ccttgcaatt
13320ctcggggttc cagcaggtat caacgggtcc cgagtgtcgc aacgagaccc tgtatctgct
13380gtacaaccgg gaaggccaga ccttggtgga gagaagctcc acctgggtga aaaaggtgat
13440ctggtatctg agcggtcgca accagaccat cctccaacgg atgccccaaa cggcttcgaa
13500accgagcgac ggaaacgtgc agatcagcgt ggaagacgcc aagatttttg gagcgcacat
13560ggtgcccaag cagaccaagc tgctacgctt cgtcgtcaac gatggcacgc gttatcagat
13620gtgtgtgatg aagctggaga gctgggccca cgtcttccgg gactacagcg tgtcttttca
13680ggtgcgattg acgttcaccg aggccaataa ccagacttac accttctgta cccatcccaa
13740tctcatcatt tgagcccgtc gcgcgcgcag ggaattttga aaaccgcgcg tcatgagtcc
13800caaagacctg acgccgttct tgacgacgtt gtggctgcta ttgggtcaca gccgcgtgcc
13860gcgggtgcgc gcagaagaat gttgcgaatt cataaacgtc aaccacccgc cggaacgctg
13920ttacgatttc aaaatgtgca atcgcttcac cgtcgcgtac gtattttcat gattgtctgc
13980gttctgtggt gcgtctggat ttgtctctcg acgtttctga tagccatgtt ccatcgacga
14040tcctcgggaa tgccagagta gattttcatg aatccacagg ctgcggtgtc cggacggcga
14100agtctgctac agtcccgaga aaacggctga gattcgcggg atcgtcacca ccatgaccca
14160ttcattgaca cgccaggtcg tacacaacaa actgacgagc tgcaactaca atccgtaagt
14220ctcttcctcg agggccttac agcctatggg agagtaagac agagagggac aaaacatcat
14280taaaaaaaaa agtctaattt cacgttttgt accccccttc ccctccgtgt tgtagcccat
14340cggccgcggc gatctcctag taacactcgt ccgacacttc caccatctcc agctcggccg
14400gcggttcggc atcctctacc agcggcgtcg tctcatcttt gccgcagcag cggacgcaca
14460ccttctccag gcagaacgcc accagctgcc gccgaacgta ccacaggtac acgtgcagac
14520ctgcgaacag gactacggag gtcatgacca ccacgacgca cacgggaatc cagggatcga
14580gattgttgct ggaactcgct atcgccaccg acgtgcccgc gtctgtctca ccgccgctcg
14640cccgatgtcg cgcggcttgt tatacgctag cccgtcgccg cctcggggca cggtgccctc
14700ctacccacgt aacttcctcc gtgacttaaa gtcgcgtgtg gtagatctcc tgctccgtgg
14760acgaaccgtc cggcaggata gcggttaagg attcggtgct aaggccgtgt cgccaacgtc
14820gaatgctacg ttgcaacagc ttcgacggac ggccatcccc tctctcatcg caataataaa
14880acaccagcag cgcgcacgac gcgatcacgg tgacacccat gattagaccc acgcagatag
14940ccagccccgc tagcgtatct agcgccatcc cgttcgctcc cgttgtctcc tgagcgaagc
15000aacttctcgg tccccgtttt caacagtttt tgtttccttc tccgcgacta gatgttaacg
15060cccgcggtct ttccggccgt gctctacctc ctggcgcttg tcgtctgggt tgagatgttc
15120tgcctcgtcg ccgtagccgt cgtcgagcgc gagatcgcct gggcgctgct gctgcggatg
15180ctggtcgttg gcctgatggt ggaagtcggc gccgccgccg cttggacctt cgtgcgttgt
15240cttgcctatc agcgctcctt ccccgtgctt acggccttcc cctgaaaccc acgttaaccg
15300accgtcccaa aaacgccggt gttaacacag gaaaaaaaga aaccacgcag gaaccgcgca
15360ggaaccacgc ggaacatggg acactatctg gaaatcctgt tcaacgtcat cgtcttcact
15420ctgctgctcg gcgtcatggt cagtatcgtc gcttggtact tcacgtgaac caccgtcgtc
15480ccggtttaaa aaccatcatc gacggccgtt ataaagccac ccggacacgc gccgcggcac
15540ttgcctacg
15549
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