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Strain-dependent requirement for IFN-γ for respiratory control and immunotherapy in murine gammaherpesvirus infection.

Abstract
Interferon-γ (IFN-γ) and perforin (pfp) are important effector mechanisms used by CD8 T cells to clear virus-infected cells. In this study, we used IFN-γ/pfp double knockout mice to address if these two effector molecules play redundant roles in the control of acute infection with murine gammaherpesvirus-68 (MHV-68) in BALB/C mice. Perforin knockout (KO) mice and wild-type mice cleared infectious virus from the lungs, even following high-dose infection. However, the IFN-γ KO and IFN-γ/pfp double knockout (DKO) groups had higher virus titers in the lungs at day 10 post-infection, and both groups had higher mortality rates. In IFN-γ/pfp DKO mice, the virus titer and mortality rate were significant higher than in IFN-γ KO mice, indicating a role for perforin in protection from disease. WT mice given IFN-γ blocking antibody also showed significantly higher viral titers. In contrast, IFN-γ KO mice on a C57BL/6 background controlled respiratory infection comparably to wild-type mice. These data show that perforin plays a redundant role in the control of virus replication, but IFN-γ plays an essential role in BALB/C mice infected with MHV-68. We conclude that there is a marked strain-dependent difference in the effector mechanisms needed to control acute MHV-68 infection between C57BL/6 and BALB/C mice. In addition we show that immune therapy that re-establishes viral control after spontaneous reactivation in CD4-deficient mice depends upon perforin in C57BL/6 mice but IFN-γ in BALB/C mice.
AuthorsChing-Yi Tsai, Zhuting Hu, Weijun Zhang, Edward J Usherwood
JournalViral immunology (Viral Immunol) Vol. 24 Issue 4 Pg. 273-80 (Aug 2011) ISSN: 1557-8976 [Electronic] United States
PMID21830899 (Publication Type: Journal Article)
Chemical References
  • Perforin
  • Interferon-gamma
Topics
  • Animals
  • Herpesviridae Infections (immunology, pathology, therapy)
  • Immunotherapy (methods)
  • Interferon-gamma (genetics, immunology)
  • Lung (virology)
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Perforin (genetics, immunology)
  • Respiratory Tract Infections (immunology, pathology, therapy)
  • Rhadinovirus (pathogenicity)
  • Rodent Diseases (immunology, pathology, therapy)
  • Survival Analysis

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