1887

Abstract

Primary infection with murine gammaherpesvirus-68 (MHV-68), as with other members of the gammaherpesvirus subfamily, is characterized by a lymphoproliferative phase. MHV-68 causes acute splenomegaly and an infectious mononucleosis-like syndrome in which there is expansion of the CD8 T cell subset. In long-term infections, MHV-68 is associated with lymphoma development. In order to elucidate the mechanisms underlying the proliferative processes, the events following infection of murine splenocytes or purified murine B lymphocytes have been examined. MHV-68 infection prolonged the viability of murine splenocytes and stimulated cellular proliferation. Unlike Epstein–Barr virus and herpesvirus saimiri, MHV-68 did not cause growth transformation. Growth transformation did not occur even when cells with a predisposition to transformation were infected or when culture conditions were selected to enhance the viability of the cells. Following MHV-68 infection, the latency-associated viral tRNAs were transcribed. However, transcription of the other known latency- associated gene, M2, was not observed. In addition, there was no evidence of productive virus replication either by staining with antibodies specific for late virus antigens or by hybridization for early and late mRNAs. In contrast to Epstein–Barr virus- and herpesvirus saimiri-infected lymphocytes, where episomal genomes are seen, Gardella gel analysis indicated that the primary lymphocytes infected by MHV-68 contained only linear virus DNA. This DNA was nuclease sensitive, indicating that, while MHV-68 was efficiently uncoated, its circularization was extremely inefficient. These results are discussed in terms of the host–virus interaction.

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1999-10-01
2020-07-10
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References

  1. Alfieri C., Birkenbach M., Kieff E.. 1991; Early events in Epstein–Barr virus infection of human B lymphocytes. Virology181:595–608
    [Google Scholar]
  2. Biesinger B., Muller-Fleckenstein I., Simmer B., Lang G., Wittmann S., Platzer E., Desrosiers R. C., Fleckenstein B.. 1992; Stable growth transformation of human T lymphocytes by herpesvirus saimiri. Proceedings of the National Academy of Sciences, USA89:3116–3119
    [Google Scholar]
  3. Blaskovic D., Stancekova M., Svobodova J., Mistrikova J.. 1980; Isolation of five strains of herpesviruses from two species of free living small rodents. Acta Virologica24:468
    [Google Scholar]
  4. Bowden R. J., Simas J. P., Davis A. J., Efstathiou S.. 1997; Murine gammaherpesvirus 68 encodes tRNA-like sequences which are expressed during latency. Journal of General Virology78:1675–1687
    [Google Scholar]
  5. Clarke A. R.. 1995; Murine models of neoplasia: functional analysis of the tumour suppressor genes Rb-1 and p53. Cancer and Metastasis Reviews14:125–148
    [Google Scholar]
  6. Clarke A. R., Maandag E. R., van Roon M., van der Lugt N. M. T., van der Valk M., Hooper M. L., Berns A., te Riele H.. 1992; Requirement for a functional Rb-1 gene in murine development. Nature359:328–330
    [Google Scholar]
  7. Clarke A. R., Purdie C. A., Harrison D. J., Morris R. G., Bird C. C., Hooper M. L., Wyllie A. H.. 1993; Thymocyte apoptosis induced by p53-dependent and independent pathways. Nature362:849–852
    [Google Scholar]
  8. Decker L. L., Klaman L. D., Thorley-Lawson D. A.. 1996a; Detection of the latent form of Epstein–Barr virus DNA in the peripheral blood of healthy individuals.Journal of. Virology70:3286–3289
    [Google Scholar]
  9. Decker L. L., Shankar P., Khan G., Freeman R. B., Dezube B. J., Lieberman J., Thorley-Lawson D. A.. 1996b; The Kaposi sarcoma-associated herpesvirus (KSHV) is present as an intact latent genome in KS tissue but replicates in the peripheral blood mononuclear cells of KS patients. Journal of Experimental Medicine184:283–288
    [Google Scholar]
  10. Efstathiou S., Ho Y. M., Minson A. C.. 1990; Cloning and molecular characterization of the murine herpesvirus 68 genome. Journal of General Virology71:1355–1364
    [Google Scholar]
  11. Ehtisham S., Sunil-Chandra N. P., Nash A. A.. 1993; Pathogenesis of murine gammaherpesvirus infection in mice deficient in CD4 and CD8 T cells. Journal of Virology67:5247–5252
    [Google Scholar]
  12. Ernberg I., Falk K., Hansson M.. 1987; Progenitor and pre-B lymphocytes transformed by Epstein–Barr virus. International Journal of Cancer39:190–197
    [Google Scholar]
  13. Fickenscher H., Fleckenstein B.. 1998; Growth transformation of human T cells. Methods in Medical Microbiology25:573–603
    [Google Scholar]
  14. Flore O., Rafii S., Ely S., O’Leary J. J., Hyjek E. M., Cesarman E.. 1998; Transformation of primary human endothelial cells by Kaposi’s sarcoma-associated herpesvirus. Nature394:588–592
    [Google Scholar]
  15. Gardella T., Medveczky P., Sairenji T., Mulder C.. 1984; Detection of circular and linear herpesvirus DNA molecules in mammalian cells by gel electrophoresis. Journal of Virology50:248–254
    [Google Scholar]
  16. Gordon J., Walker L., Guy G., Brown G., Rowe M., Rickinson A.. 1986; Control of human B-lymphocyte replication. II. Transforming Epstein–Barr virus exploits three distinct viral signals to undermine three separate control points in B- cell growth. Immunology58:591–595
    [Google Scholar]
  17. Hurley E. A., Thorley-Lawson D. A.. 1988; B cell activation and the establishment of Epstein–Barr virus latency. Journal of Experimental Medicine168:2059–2075
    [Google Scholar]
  18. Husain S. M., Usherwood E. J., Dyson H., Coleclough C., Cappola M., Woodland D. L., Blackman M., Stewart J. P., Sample J. T.. 1999; Murine gammaherpesvirus M2 gene is latency associated and a target for CD8+ T lymphocytes. Proceedings of the National Academy of Sciences, USA96:7508–7513
    [Google Scholar]
  19. Jamieson D. R. S., Robinson L. H., Daksis J. I., Nicholl M. J., Preston C. M.. 1995; Quiescent viral genomes in human fibroblasts after infection with herpes simplex virus type 1 Vmw65 mutants. Journal of General Virology76:1417–1431
    [Google Scholar]
  20. Nash A. A., Usherwood E. J., Stewart J. P.. 1996; Immunological features of murine gammaherpesvirus infection. Seminars in Virology7:125–130
    [Google Scholar]
  21. Raab-Traub N.. 1996; Pathogenesis of Epstein–Barr virus and its associated malignancies. Seminars in Virology7:315–323
    [Google Scholar]
  22. Rickinson A. B., Kieff E.. 1996; Epstein–Barr virus. In Field’s Virology pp2397–2446 Edited by Fields B. N., Knipe D. M., Howley P. M.. Philadelphia: Lippincott–Raven;
    [Google Scholar]
  23. Roizman B., Sears A. E.. 1996; Herpes simplex viruses and their replication. In Field’s Virology pp2231–2295 Edited by Fields B. N., Knipe D. M., Howley P. M. Philadelphia: Lippincott–Raven;
    [Google Scholar]
  24. Roizmann B., Desrosiers R. C., Fleckenstein B., Lopez C., Minson A. C., Studdert M. J.. 1992; The family Herpesviridae : an update. The Herpesvirus Study Group of the International Committee on Taxonomy of Viruses. Archives of Virology123:425–449
    [Google Scholar]
  25. Schirm S., Muller I., Desrosiers R. C., Fleckenstein B.. 1984; Herpesvirus saimiri DNA in a lymphoid cell line established by in vitro transformation. Journal of Virology49:938–946
    [Google Scholar]
  26. Schulz T. F.. 1998; Kaposi’s sarcoma-associated herpesvirus (human herpesvirus-8. Journal of General Virology79:1573–1591
    [Google Scholar]
  27. Sinclair A. J., Farrell P. J.. 1995; Host cell requirements for efficient infection of quiescent primary B lymphocytes by Epstein–Barr virus. Journal of Virology69:5461–5468
    [Google Scholar]
  28. Stevenson P. G., Doherty P. C.. 1999; Non-antigen-specific B-cell activation following murine gammaherpesvirus infection is CD4 independent in vitro but CD4 dependent in vivo. Journal of Virology73:1075–1079
    [Google Scholar]
  29. Stewart J. P., Usherwood E. J., Ross A., Dyson H., Nash T.. 1998; Lung epithelial cells are a major site of murine gammaherpesvirus persistence. Journal of Experimental Medicine187:1941–1951
    [Google Scholar]
  30. Stuart A. D., Stewart J. P., Arrand J. R., Mackett M.. 1995; The Epstein–Barr virus encoded cytokine viral interleukin-10 enhances transformation of human B lymphocytes. Oncogene11:1711–1719
    [Google Scholar]
  31. Sunil-Chandra N. P., Efstathiou S., Arno J., Nash A. A.. 1992a; Virological and pathological features of mice infected with murine gammaherpesvirus 68. Journal of General Virology73:2347–2356
    [Google Scholar]
  32. Sunil-Chandra N. P., Efstathiou S., Nash A. A.. 1992b; Murine gammaherpesvirus 68 establishes a latent infection in mouse B lymphocytes in vivo. Journal of General Virology73:3275–3279
    [Google Scholar]
  33. Sunil-Chandra N. P., Efstathiou S., Nash A. A.. 1993; Interactions of murine gammaherpesvirus 68 with B and T cell lines. Virology193:825–833
    [Google Scholar]
  34. Sunil-Chandra N. P., Arno J., Fazakerley J., Nash A. A.. 1994; Lymphoproliferative disease in mice infected with murine gammaherpesvirus 68. American Journal of Pathology145:818–826
    [Google Scholar]
  35. Tripp R. A., Hamilton-Easton A. M., Cardin R. D., Nguyen P., Behm F. G., Woodland D. L., Doherty P. C., Blackman M. A.. 1997; Pathogenesis of an infectious mononucleosis-like disease induced by a murine gamma- herpesvirus: role for a viral superantigen?. Journal of Experimental Medicine185:1641–1650
    [Google Scholar]
  36. Umene K., Nishimoto T.. 1996; Replication of herpes simplex virus type 1 DNA is inhibited in a temperature-sensitive mutant of BHK- 21 cells lacking RCC1 (regulator of chromosome condensation) and virus DNA remains linear. Journal of General Virology77:2261–2270
    [Google Scholar]
  37. Usherwood E. J., Ross A. J., Allen D. J., Nash A. A.. 1996a; Murine gammaherpesvirus- induced splenomegaly: a critical role for CD4 T cells. Journal of General Virology77:627–630
    [Google Scholar]
  38. Usherwood E. J., Stewart J. P., Nash A. A.. 1996b; Characterization of tumor cell lines derived from murine gammaherpesvirus-68-infected mice. Journal of Virology70:6516–6518
    [Google Scholar]
  39. Weck K. E., Kim S. S., Virgin H. W.IV., Speck S. H.. 1999; Macrophages are the major reservoir of latent murine gammaherpesvirus 68 in peritoneal cells.Journal of. Virology73:3273–3283
    [Google Scholar]
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