1887

Abstract

Murine gammaherpesvirus 68 (MHV-68) encodes a set of unique genes, M1, M2, M3 and M4, and eight non-translated tRNA-like molecules that are thought to be important in virus–host interactions and latent infection. The M4 gene is predicted to encode a novel secreted protein. To investigate the role of M4 in viral pathogenesis, a mutant MHV-68 that did not express M4 was constructed and its replication was characterized and . Virus replication was identical to the wild type and no difference could be detected in virus replication in the lung following intranasal infection. However, in the spleen, virus deficient in M4 expression was severely attenuated in the establishment of latency. These results indicate a critical role for M4 in MHV-68 pathogenesis.

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2006-04-01
2024-03-29
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References

  1. Adler H., Messerle M., Wagner M., Koszinowski U. H. 2000; Cloning and mutagenesis of the murine gammaherpesvirus 68 genome as an infectious bacterial artificial chromosome. J Virol 74:6964–6974 [CrossRef]
    [Google Scholar]
  2. Bowden R. J., Simas J. P., Davis A. J., Efstathiou S. 1997; Murine gammaherpesvirus 68 encodes tRNA-like sequences which are expressed during latency. J Gen Virol 78:1675–1687
    [Google Scholar]
  3. Bridgeman A., Stevenson P. G., Simas J. P., Efstathiou S. 2001; A secreted chemokine binding protein encoded by murine gammaherpesvirus-68 is necessary for the establishment of a normal latent load. J Exp Med 194:301–312 [CrossRef]
    [Google Scholar]
  4. Clambey E. T., Virgin H. W. IV, Speck S. H. 2000; Disruption of the murine gammaherpesvirus 68 M1 open reading frame leads to enhanced reactivation from latency. J Virol 74:1973–1984 [CrossRef]
    [Google Scholar]
  5. Coleman H. M., Efstathiou S., Stevenson P. G. 2005; Transcription of the murine gammaherpesvirus 68 ORF73 from promoters in the viral terminal repeats. J Gen Virol 86:561–574 [CrossRef]
    [Google Scholar]
  6. DeLuca N. A., Schaffer P. A. 1987; Activities of herpes simplex virus type 1 (HSV-1) ICP4 genes specifying nonsense peptides. Nucleic Acids Res 15:4491–4511 [CrossRef]
    [Google Scholar]
  7. Dutia B. M., Roy D. J., Ebrahimi B., Gangadharan B., Efstathiou S., Stewart J. P., Nash A. A. 2004; Identification of a region of the virus genome involved in murine gammaherpesvirus 68-induced splenic pathology. J Gen Virol 85:1393–1400 [CrossRef]
    [Google Scholar]
  8. Ebrahimi B., Dutia B. M., Roberts K. L., Garcia-Ramirez J. J., Dickinson P., Stewart J. P., Ghazal P., Roy D. J., Nash A. A. 2003; Transcriptome profile of murine gammaherpesvirus-68 lytic infection. J Gen Virol 84:99–109 [CrossRef]
    [Google Scholar]
  9. Efstathiou S., Ho Y. M., Minson A. C. 1990; Cloning and molecular characterization of the murine herpesvirus 68 genome. J Gen Virol 71:1355–1364 [CrossRef]
    [Google Scholar]
  10. Evans A. G., Moorman N. J., Willer D. O., Speck S. H. 2006; The M4 gene of γ HV68 encodes a secreted glycoprotein and is required for the efficient establishment of splenic latency. Virology 344:520–531 [CrossRef]
    [Google Scholar]
  11. Fowler P., Marques S., Simas J. P., Efstathiou S. 2003; ORF73 of murine herpesvirus-68 is critical for the establishment and maintenance of latency. J Gen Virol 84:3405–3416 [CrossRef]
    [Google Scholar]
  12. Jacoby M. A., Virgin H. W. IV, Speck S. H. 2002; Disruption of the M2 gene of murine gammaherpesvirus 68 alters splenic latency following intranasal, but not intraperitoneal, inoculation. J Virol 76:1790–1801 [CrossRef]
    [Google Scholar]
  13. Macrae A. I., Dutia B. M., Milligan S., Brownstein D. G., Allen D. J., Mistrikova J., Davison A. J., Nash A. A., Stewart J. P. 2001; Analysis of a novel strain of murine gammaherpesvirus reveals a genomic locus important for acute pathogenesis. J Virol 75:5315–5327 [CrossRef]
    [Google Scholar]
  14. Macrae A. I., Usherwood E. J., Husain S. M. & 7 other authors 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 [CrossRef]
    [Google Scholar]
  15. Marques S., Efstathiou S., Smith K. G., Haury M., Simas J. P. 2003; Selective gene expression of latent murine gammaherpesvirus 68 in B lymphocytes. J Virol 77:7308–7318 [CrossRef]
    [Google Scholar]
  16. Messerle M., Crnkovic I., Hammerschmidt W., Ziegler H., Koszinowski U. H. 1997; Cloning and mutagenesis of a herpesvirus genome as an infectious bacterial artificial chromosome. Proc Natl Acad Sci U S A 94:14759–14763 [CrossRef]
    [Google Scholar]
  17. Nash A. A., Dutia B. M., Stewart J. P., Davison A. J. 2001; Natural history of murine γ -herpesvirus infection. Philos Trans R Soc Lond B Biol Sci 356:569–579 [CrossRef]
    [Google Scholar]
  18. Parry C. M., Simas J. P., Smith V. P., Stewart C. A., Minson A. C., Efstathiou S., Alcami A. 2000; A broad spectrum secreted chemokine binding protein encoded by a herpesvirus. J Exp Med 191:573–578 [CrossRef]
    [Google Scholar]
  19. Pfeffer S., Sewer A., Lagos-Quintana M. & 16 other authors 2005; Identification of microRNAs of the herpesvirus family. Nat Methods 2:269–276 [CrossRef]
    [Google Scholar]
  20. Simas J. P., Efstathiou S. 1998; Murine gammaherpesvirus 68: a model for the study of gammaherpesvirus pathogenesis. Trends Microbiol 6:276–282 [CrossRef]
    [Google Scholar]
  21. Simas J. P., Marques S., Bridgeman A., Efstathiou S., Adler H. 2004; The M2 gene product of murine gammaherpesvirus 68 is required for efficient colonization of splenic follicles but is not necessary for expansion of latently infected germinal centre B cells. J Gen Virol 85:2789–2797 [CrossRef]
    [Google Scholar]
  22. Sunil-Chandra N. P., Efstathiou S., Arno J., Nash A. A. 1992a; Virological and pathological features of mice infected with murine gammaherpesvirus 68. J Gen Virol 73:2347–2356 [CrossRef]
    [Google Scholar]
  23. Sunil-Chandra N. P., Efstathiou S., Nash A. A. 1992b; Murine gammaherpesvirus 68 establishes a latent infection in mouse B lymphocytes in vivo . J Gen Virol 73:3275–3279 [CrossRef]
    [Google Scholar]
  24. Townsley A. C., Dutia B. M., Nash A. A. 2004; The M4 gene of murine gammaherpesvirus modulates productive and latent infection in vivo. J Virol 78:758–767 [CrossRef]
    [Google Scholar]
  25. van Berkel V., Barrett J., Tiffany H. L., Fremont D. H., Murphy P. M., McFadden G., Speck S. H., Virgin H. W. IV 2000; Identification of a gammaherpesvirus selective chemokine binding protein that inhibits chemokine action. J Virol 74:6741–6747 [CrossRef]
    [Google Scholar]
  26. van Berkel V., Levine B., Kapadia S. B., Goldman J. E., Speck S. H., Virgin H. W. IV 2002; Critical role for a high-affinity chemokine-binding protein in γ -herpesvirus-induced lethal meningitis. J Clin Invest 109:905–914 [CrossRef]
    [Google Scholar]
  27. Virgin H. W. IV, Speck S. H. 1999; Unraveling immunity to γ -herpesviruses: a new model for understanding the role of immunity in chronic virus infection. Curr Opin Immunol 11:371–379 [CrossRef]
    [Google Scholar]
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