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. 1997 May;71(5):3916–3921. doi: 10.1128/jvi.71.5.3916-3921.1997

Gamma interferon is not essential for recovery from acute infection with murine gammaherpesvirus 68.

S R Sarawar 1, R D Cardin 1, J W Brooks 1, M Mehrpooya 1, A M Hamilton-Easton 1, X Y Mo 1, P C Doherty 1
PMCID: PMC191543  PMID: 9094668

Abstract

Murine gammaherpesvirus 68 (MHV-68) when administered intranasally induces high levels of gamma interferon (IFN-gamma) in the lymphoid tissues of infected mice. In order to investigate the role of this cytokine in the immune response to MHV-68, mice which were congenitally deficient in the IFN-gamma gene (IFN-gamma knockout mice) were infected with the virus. Comparison of the courses of the disease in wild-type control and IFN-gamma knockout mice revealed surprisingly little difference. Both groups of mice had cleared infectious virus from the lungs 15 days after infection, although there did appear to be a slight delay in viral clearance in the IFN-gamma knockout mice. In addition, after the initial phase of viral clearance, the lungs of both groups remained clear of replicating virus throughout the course of the experiment, which concluded 34 days after infection. Consistent with these observations, cytotoxic T-cell activities were similar in the two groups of mice. Levels of latent virus were comparable in wild-type and knockout mice over the time course studied. Furthermore, analysis of the numbers, types, and activation status of cells in the lungs, lymph nodes, and spleens of control and knockout mice revealed no striking difference. This suggests that IFN-gamma is not essential for regulating the cell recruitment or proliferation that normally occurs during this viral infection. Apart from the expected lack of IFN-gamma, cytokine profiles were not dramatically altered in IFN-gamma knockout mice, demonstrating that IFN-gamma did not suppress the proliferation or differentiation of Th2 cells during MHV-68 infection. These observations indicate that IFN-gamma plays a nonessential or redundant role in the control of acute infection with MHV-68.

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Selected References

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  1. Allan W., Tabi Z., Cleary A., Doherty P. C. Cellular events in the lymph node and lung of mice with influenza. Consequences of depleting CD4+ T cells. J Immunol. 1990 May 15;144(10):3980–3986. [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. Bouley D. M., Kanangat S., Wire W., Rouse B. T. Characterization of herpes simplex virus type-1 infection and herpetic stromal keratitis development in IFN-gamma knockout mice. J Immunol. 1995 Oct 15;155(8):3964–3971. [PubMed] [Google Scholar]
  4. Cardin R. D., Brooks J. W., Sarawar S. R., Doherty P. C. Progressive loss of CD8+ T cell-mediated control of a gamma-herpesvirus in the absence of CD4+ T cells. J Exp Med. 1996 Sep 1;184(3):863–871. doi: 10.1084/jem.184.3.863. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dalton D. K., Pitts-Meek S., Keshav S., Figari I. S., Bradley A., Stewart T. A. Multiple defects of immune cell function in mice with disrupted interferon-gamma genes. Science. 1993 Mar 19;259(5102):1739–1742. doi: 10.1126/science.8456300. [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. 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]
  8. Gajewski T. F., Joyce J., Fitch F. W. Antiproliferative effect of IFN-gamma in immune regulation. III. Differential selection of TH1 and TH2 murine helper T lymphocyte clones using recombinant IL-2 and recombinant IFN-gamma. J Immunol. 1989 Jul 1;143(1):15–22. [PubMed] [Google Scholar]
  9. Graham M. B., Dalton D. K., Giltinan D., Braciale V. L., Stewart T. A., Braciale T. J. Response to influenza infection in mice with a targeted disruption in the interferon gamma gene. J Exp Med. 1993 Nov 1;178(5):1725–1732. doi: 10.1084/jem.178.5.1725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lucin P., Pavić I., Polić B., Jonjić S., Koszinowski U. H. Gamma interferon-dependent clearance of cytomegalovirus infection in salivary glands. J Virol. 1992 Apr;66(4):1977–1984. doi: 10.1128/jvi.66.4.1977-1984.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Sarawar S. R., Cardin R. D., Brooks J. W., Mehrpooya M., Tripp R. A., Doherty P. C. Cytokine production in the immune response to murine gammaherpesvirus 68. J Virol. 1996 May;70(5):3264–3268. doi: 10.1128/jvi.70.5.3264-3268.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Sarawar S. R., Doherty P. C. Concurrent production of interleukin-2, interleukin-10, and gamma interferon in the regional lymph nodes of mice with influenza pneumonia. J Virol. 1994 May;68(5):3112–3119. doi: 10.1128/jvi.68.5.3112-3119.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Schijns V. E., Haagmans B. L., Rijke E. O., Huang S., Aguet M., Horzinek M. C. IFN-gamma receptor-deficient mice generate antiviral Th1-characteristic cytokine profiles but altered antibody responses. J Immunol. 1994 Sep 1;153(5):2029–2037. [PubMed] [Google Scholar]
  14. Smith P. M., Wolcott R. M., Chervenak R., Jennings S. R. Control of acute cutaneous herpes simplex virus infection: T cell-mediated viral clearance is dependent upon interferon-gamma (IFN-gamma). Virology. 1994 Jul;202(1):76–88. doi: 10.1006/viro.1994.1324. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Sunil-Chandra N. P., Efstathiou S., Nash A. A. Interactions of murine gammaherpesvirus 68 with B and T cell lines. Virology. 1993 Apr;193(2):825–833. doi: 10.1006/viro.1993.1191. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Wille A., Gessner A., Lother H., Lehmann-Grube F. Mechanism of recovery from acute virus infection. VIII. Treatment of lymphocytic choriomeningitis virus-infected mice with anti-interferon-gamma monoclonal antibody blocks generation of virus-specific cytotoxic T lymphocytes and virus elimination. Eur J Immunol. 1989 Jul;19(7):1283–1288. doi: 10.1002/eji.1830190720. [DOI] [PubMed] [Google Scholar]

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