Complete sequence and genomic analysis of murine gammaherpesvirus 68

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J. Virol., Aug 1997, 5894-5904, Vol 71, No. 8
Copyright © 1997, American Society for Microbiology

Complete sequence and genomic analysis of murine gammaherpesvirus 68

HW Virgin 4th, P Latreille, P Wamsley, K Hallsworth, KE Weck, AJ Dal Canto and SH Speck
Department of Pathology and Center for Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

Murine gammaherpesvirus 68 (gammaHV68) infects mice, thus providing a tractable small-animal model for analysis of the acute and chronic pathogenesis of gammaherpesviruses. To facilitate molecular analysis of gammaHV68 pathogenesis, we have sequenced the gammaHV68 genome. The genome contains 118,237 bp of unique sequence flanked by multiple copies of a 1,213-bp terminal repeat. The GC content of the unique portion of the genome is 46%, while the GC content of the terminal repeat is 78%. The unique portion of the genome is estimated to encode at least 80 genes and is largely colinear with the genomes of Kaposi's sarcoma herpesvirus (KSHV; also known as human herpesvirus 8), herpesvirus saimiri (HVS), and Epstein-Barr virus (EBV). We detected 63 open reading frames (ORFs) homologous to HVS and KSHV ORFs and used the HVS/KSHV numbering system to designate these ORFs. gammaHV68 shares with HVS and KSHV ORFs homologous to a complement regulatory protein (ORF 4), a D-type cyclin (ORF 72), and a G-protein-coupled receptor with close homology to the interleukin-8 receptor (ORF 74). One ORF (K3) was identified in gammaHV68 as homologous to both ORFs K3 and K5 of KSHV and contains a domain found in a bovine herpesvirus 4 major immediate-early protein. We also detected 16 methionine-initiated ORFs predicted to encode proteins at least 100 amino acids in length that are unique to gammaHV68 (ORFs M1 to 14). ORF M1 has striking homology to poxvirus serpins, while ORF M11 encodes a potential homolog of Bcl-2- like molecules encoded by other gammaherpesviruses (gene 16 of HVS and KSHV and the BHRF1 gene of EBV). In addition, clustered at the left end of the unique region are eight sequences with significant homology to bacterial tRNAs. The unique region of the genome contains two internal repeats: a 40-bp repeat located between bp 26778 and 28191 in the genome and a 100-bp repeat located between bp 98981 and 101170. Analysis of the gammaHV68, HVS, EBV, and KSHV genomes demonstrated that each of these viruses have large colinear gene blocks interspersed by regions containing virus-specific ORFs. Interestingly, genes associated with EBV cell tropism, latency, and transformation are all contained within these regions encoding virus-specific genes. This finding suggests that pathogenesis-associated genes of gammaherpesviruses, including gammaHV68, may be contained in similarly positioned genome regions. The availability of the gammaHV68 genomic sequence will facilitate analysis of critical issues in gammaherpesvirus biology via integration of molecular and pathogenetic studies in a small-animal model.

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Macrae, A. I., Usherwood, E. J., Husain, S. M., Flano, E., Kim, I.-J., Woodland, D. L., Nash, A. A., Blackman, M. A., Sample, J. T., Stewart, J. P. (2003). Murid Herpesvirus 4 Strain 68 M2 Protein Is a B-Cell-Associated Antigen Important for Latency but Not Lymphocytosis. J. Virol. 77: 9700-9709 [Abstract] [Full Text]
Kim, I.-J., Flano, E., Woodland, D. L., Lund, F. E., Randall, T. D., Blackman, M. A. (2003). Maintenance of Long Term {gamma}-Herpesvirus B Cell Latency Is Dependent on CD40-Mediated Development of Memory B Cells. J. Immunol. 171: 886-892 [Abstract] [Full Text]
Dourmishev, L. A., Dourmishev, A. L., Palmeri, D., Schwartz, R. A., Lukac, D. M. (2003). Molecular Genetics of Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Epidemiology and Pathogenesis. Microbiol. Mol. Biol. Rev. 67: 175-212 [Abstract] [Full Text]
Perelygina, L., Zhu, L., Zurkuhlen, H., Mills, R., Borodovsky, M., Hilliard, J. K. (2003). Complete Sequence and Comparative Analysis of the Genome of Herpes B Virus (Cercopithecine Herpesvirus 1) from a Rhesus Monkey. J. Virol. 77: 6167-6177 [Abstract] [Full Text]
Pavlova, I. V., Virgin, H. W. IV, Speck, S. H. (2003). Disruption of Gammaherpesvirus 68 Gene 50 Demonstrates that Rta Is Essential for Virus Replication. J. Virol. 77: 5731-5739 [Abstract] [Full Text]
Rose, T. M., Ryan, J. T., Schultz, E. R., Raden, B. W., Tsai, C.-C. (2003). Analysis of 4.3 Kilobases of Divergent Locus B of Macaque Retroperitoneal Fibromatosis-Associated Herpesvirus Reveals a Close Similarity in Gene Sequence and Genome Organization to Kaposi's Sarcoma-Associated Herpesvirus. J. Virol. 77: 5084-5097 [Abstract] [Full Text]
van Dyk, L. F., Virgin, H. W. IV, Speck, S. H. (2003). Maintenance of Gammaherpesvirus Latency Requires Viral Cyclin in the Absence of B Lymphocytes. J. Virol. 77: 5118-5126 [Abstract] [Full Text]
Flano, E., Kim, I.-J., Moore, J., Woodland, D. L., Blackman, M. A. (2003). Differential {gamma}-Herpesvirus Distribution in Distinct Anatomical Locations and Cell Subsets During Persistent Infection in Mice. J. Immunol. 170: 3828-3834 [Abstract] [Full Text]
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Spiller, O. B., Blackbourn, D. J., Mark, L., Proctor, D. G., Blom, A. M. (2003). Functional Activity of the Complement Regulator Encoded by Kaposi's Sarcoma-associated Herpesvirus. J. Biol. Chem. 278: 9283-9289 [Abstract] [Full Text]

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