Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1996 Oct;70(10):6775–6780. doi: 10.1128/jvi.70.10.6775-6780.1996

Mature B cells are required for acute splenic infection, but not for establishment of latency, by murine gammaherpesvirus 68.

K E Weck 1, M L Barkon 1, L I Yoo 1, S H Speck 1, I V Virgin HW 1
PMCID: PMC190721  PMID: 8794315

Abstract

Murine gammaherpesvirus 68 (gamma HV-68; also referred to as MHV-68) is a gammaherpesvirus which infects murid rodents. Previous studies showed that CD8 T cells are important for controlling gamma HV-68 replication during the first 2 weeks of infection and suggested a role for B cells in latent or persistent gamma HV-68 infection. To further define the importance of B cells and CD8 T cells during acute and chronic gamma HV-68 infection, we examined splenic infection in mice with null mutations in the transmembrane domain of the mu-heavy-chain constant region (MuMT; B-cell and antibody deficient) or in the beta2-microglobulin gene (beta2 -/-; CD8 deficient). Immunocompetent mice infected intraperitoneally with gamma HV-68 demonstrated peak splenic titers 9 to 10 days postinfection, cleared infectious virus 15 to 20 days postinfection, and harbored low levels of latent virus at 6 weeks postinfection. Beta2-/- mice showed peak splenic gamma HV-68 titers similar to those of normal mice but were unable to clear infectious virus completely from the spleen, demonstrating persistent infectious virus 6 weeks postinfection. These data indicate that CD8 T cells are important for clearing infectious gamma HV-68 from the spleen. Infected MuMT mice did not demonstrate detectable infectious gamma HV-68 in the spleen at any time after infection, indicating that mature B lymphocytes are necessary for acute splenic infection by gamma HV-68. Despite the lack of measurable acute infection, MuMT spleen cells harbored latent virus 6 weeks postinfection at a level about 100-fold higher than that in normal mice. These data demonstrate establishment of latency by a herpesvirus in an organ in the absence of acute viral replication in that organ. In addition, they demonstrate that gamma HV-68 can establish latency in a cell type other than mature B lymphocytes.

Full Text

The Full Text of this article is available as a PDF (208.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Battegay M., Moskophidis D., Waldner H., Bründler M. A., Fung-Leung W. P., Mak T. W., Hengartner H., Zinkernagel R. M. Impairment and delay of neutralizing antiviral antibody responses by virus-specific cytotoxic T cells. J Immunol. 1993 Nov 15;151(10):5408–5415. [PubMed] [Google Scholar]
  2. Blaskovic D., Stanceková M., Svobodová J., Mistríková J. Isolation of five strains of herpesviruses from two species of free living small rodents. Acta Virol. 1980 Dec;24(6):468–468. [PubMed] [Google Scholar]
  3. Blaskovic D., Staneková D., Rajcáni J. Experimental pathogenesis of murine herpesvirus in newborn mice. Acta Virol. 1984 May;28(3):225–231. [PubMed] [Google Scholar]
  4. Cook J. R., Solheim J. C., Connolly J. M., Hansen T. H. Induction of peptide-specific CD8+ CTL clones in beta 2-microglobulin-deficient mice. J Immunol. 1995 Jan 1;154(1):47–57. [PubMed] [Google Scholar]
  5. Doherty P. C., Hou S., Southern P. J. Lymphocytic choriomeningitis virus induces a chronic wasting disease in mice lacking class I major histocompatibility complex glycoproteins. J Neuroimmunol. 1993 Jul;46(1-2):11–17. doi: 10.1016/0165-5728(93)90228-q. [DOI] [PubMed] [Google Scholar]
  6. Efstathiou S., Ho Y. M., Hall S., Styles C. J., Scott S. D., Gompels U. A. Murine herpesvirus 68 is genetically related to the gammaherpesviruses Epstein-Barr virus and herpesvirus saimiri. J Gen Virol. 1990 Jun;71(Pt 6):1365–1372. doi: 10.1099/0022-1317-71-6-1365. [DOI] [PubMed] [Google Scholar]
  7. Efstathiou S., Ho Y. M., Minson A. C. Cloning and molecular characterization of the murine herpesvirus 68 genome. J Gen Virol. 1990 Jun;71(Pt 6):1355–1364. doi: 10.1099/0022-1317-71-6-1355. [DOI] [PubMed] [Google Scholar]
  8. Ehtisham S., Sunil-Chandra N. P., Nash A. A. Pathogenesis of murine gammaherpesvirus infection in mice deficient in CD4 and CD8 T cells. J Virol. 1993 Sep;67(9):5247–5252. doi: 10.1128/jvi.67.9.5247-5252.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fiette L., Aubert C., Brahic M., Rossi C. P. Theiler's virus infection of beta 2-microglobulin-deficient mice. J Virol. 1993 Jan;67(1):589–592. doi: 10.1128/jvi.67.1.589-592.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gratama J. W., Lennette E. T., Lönnqvist B., Oosterveer M. A., Klein G., Ringdén O., Ernberg I. Detection of multiple Epstein-Barr viral strains in allogeneic bone marrow transplant recipients. J Med Virol. 1992 May;37(1):39–47. doi: 10.1002/jmv.1890370107. [DOI] [PubMed] [Google Scholar]
  11. Gratama J. W., Oosterveer M. A., Lepoutre J. M., van Rood J. J., Zwaan F. E., Vossen J. M., Kapsenberg J. G., Richel D., Klein G., Ernberg I. Serological and molecular studies of Epstein-Barr virus infection in allogeneic marrow graft recipients. Transplantation. 1990 Apr;49(4):725–730. doi: 10.1097/00007890-199004000-00014. [DOI] [PubMed] [Google Scholar]
  12. Gratama J. W., Oosterveer M. A., Lepoutre J., van Rood J. J., Zwaan F. E., Vossen J. M., Kapsenberg J. G., Klein G., Ernberg I. Persistence and transfer of Epstein-Barr virus after allogeneic bone marrow transplantation. Transplant Proc. 1989 Feb;21(1 Pt 3):3097–3098. [PubMed] [Google Scholar]
  13. Gratama J. W., Oosterveer M. A., Zwaan F. E., Lepoutre J., Klein G., Ernberg I. Eradication of Epstein-Barr virus by allogeneic bone marrow transplantation: implications for sites of viral latency. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8693–8696. doi: 10.1073/pnas.85.22.8693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gratama J. W., Zutter M. M., Minarovits J., Oosterveer M. A., Thomas E. D., Klein G., Ernberg I. Expression of Epstein-Barr virus-encoded growth-transformation-associated proteins in lymphoproliferations of bone-marrow transplant recipients. Int J Cancer. 1991 Jan 21;47(2):188–192. doi: 10.1002/ijc.2910470205. [DOI] [PubMed] [Google Scholar]
  15. Hou S., Doherty P. C., Zijlstra M., Jaenisch R., Katz J. M. Delayed clearance of Sendai virus in mice lacking class I MHC-restricted CD8+ T cells. J Immunol. 1992 Aug 15;149(4):1319–1325. [PubMed] [Google Scholar]
  16. Hou S., Fishman M., Murti K. G., Doherty P. C. Divergence between cytotoxic effector function and tumor necrosis factor alpha production for inflammatory CD4+ T cells from mice with Sendai virus pneumonia. J Virol. 1993 Oct;67(10):6299–6302. doi: 10.1128/jvi.67.10.6299-6302.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hyland L., Hou S., Coleclough C., Takimoto T., Doherty P. C. Mice lacking CD8+ T cells develop greater numbers of IgA-producing cells in response to a respiratory virus infection. Virology. 1994 Oct;204(1):234–241. doi: 10.1006/viro.1994.1527. [DOI] [PubMed] [Google Scholar]
  18. Kitamura D., Roes J., Kühn R., Rajewsky K. A B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin mu chain gene. Nature. 1991 Apr 4;350(6317):423–426. doi: 10.1038/350423a0. [DOI] [PubMed] [Google Scholar]
  19. Koller B. H., Marrack P., Kappler J. W., Smithies O. Normal development of mice deficient in beta 2M, MHC class I proteins, and CD8+ T cells. Science. 1990 Jun 8;248(4960):1227–1230. doi: 10.1126/science.2112266. [DOI] [PubMed] [Google Scholar]
  20. Lehmann-Grube F., Dralle H., Utermöhlen O., Löhler J. MHC class I molecule-restricted presentation of viral antigen in beta 2-microglobulin-deficient mice. J Immunol. 1994 Jul 15;153(2):595–603. [PubMed] [Google Scholar]
  21. Lehmann-Grube F., Löhler J., Utermöhlen O., Gegin C. Antiviral immune responses of lymphocytic choriomeningitis virus-infected mice lacking CD8+ T lymphocytes because of disruption of the beta 2-microglobulin gene. J Virol. 1993 Jan;67(1):332–339. doi: 10.1128/jvi.67.1.332-339.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Levitskaya J., Coram M., Levitsky V., Imreh S., Steigerwald-Mullen P. M., Klein G., Kurilla M. G., Masucci M. G. Inhibition of antigen processing by the internal repeat region of the Epstein-Barr virus nuclear antigen-1. Nature. 1995 Jun 22;375(6533):685–688. doi: 10.1038/375685a0. [DOI] [PubMed] [Google Scholar]
  23. Matloubian M., Concepcion R. J., Ahmed R. CD4+ T cells are required to sustain CD8+ cytotoxic T-cell responses during chronic viral infection. J Virol. 1994 Dec;68(12):8056–8063. doi: 10.1128/jvi.68.12.8056-8063.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Mistríková J., Blaskovic D. Ecology of the murine alphaherpesvirus and its isolation from lungs of rodents in cell culture. Acta Virol. 1985 Jul;29(4):312–317. [PubMed] [Google Scholar]
  25. Muller D., Koller B. H., Whitton J. L., LaPan K. E., Brigman K. K., Frelinger J. A. LCMV-specific, class II-restricted cytotoxic T cells in beta 2-microglobulin-deficient mice. Science. 1992 Mar 20;255(5051):1576–1578. doi: 10.1126/science.1347959. [DOI] [PubMed] [Google Scholar]
  26. Pollock J. L., Virgin H. W., 4th Latency, without persistence, of murine cytomegalovirus in the spleen and kidney. J Virol. 1995 Mar;69(3):1762–1768. doi: 10.1128/jvi.69.3.1762-1768.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rajcáni J., Blaskovic D., Svobodová J., Ciampor F., Hucková D., Staneková D. Pathogenesis of acute and persistent murine herpesvirus infection in mice. Acta Virol. 1985 Jan;29(1):51–60. [PubMed] [Google Scholar]
  28. Rodriguez M., Dunkel A. J., Thiemann R. L., Leibowitz J., Zijlstra M., Jaenisch R. Abrogation of resistance to Theiler's virus-induced demyelination in H-2b mice deficient in beta 2-microglobulin. J Immunol. 1993 Jul 1;151(1):266–276. [PubMed] [Google Scholar]
  29. Stewart J. P., Janjua N. J., Sunil-Chandra N. P., Nash A. A., Arrand J. R. Characterization of murine gammaherpesvirus 68 glycoprotein B (gB) homolog: similarity to Epstein-Barr virus gB (gp110). J Virol. 1994 Oct;68(10):6496–6504. doi: 10.1128/jvi.68.10.6496-6504.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sunil-Chandra N. P., Efstathiou S., Arno J., Nash A. A. Virological and pathological features of mice infected with murine gamma-herpesvirus 68. J Gen Virol. 1992 Sep;73(Pt 9):2347–2356. doi: 10.1099/0022-1317-73-9-2347. [DOI] [PubMed] [Google Scholar]
  31. Sunil-Chandra N. P., Efstathiou S., Nash A. A. Murine gammaherpesvirus 68 establishes a latent infection in mouse B lymphocytes in vivo. J Gen Virol. 1992 Dec;73(Pt 12):3275–3279. doi: 10.1099/0022-1317-73-12-3275. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES