Gamma interferon plays a crucial early antiviral role in protection against West Nile virus infection

Bimmi Shrestha, Tian Wang, Melanie A. Samuel, Kevin Whitby, Joe Craft, Erol Fikrig, Michael S. Diamond

Research output: Contribution to journalArticle

137 Scopus citations

Abstract

West Nile virus (WNV) causes a severe central nervous system (CNS) infection in humans, primarily in the elderly and immunocompromised. Prior studies have established an essential protective role of several innate immune response elements, including alpha/beta interferon (IFN-α/β), immunoglobulin M, γδ T cells, and complement against WNV infection. In this study, we demonstrate that a lack of IFN-γ production or signaling results in increased vulnerability to lethal WNV infection by a subcutaneous route in mice, with a rise in mortality from 30% (wild-type mice) to 90% (IFN-γ-/- or IFN-γR-/- mice) and a decrease in the average survival time. This survival pattern in IFN-γ-/- and IFN-γR-/- mice correlated with higher viremia and greater viral replication in lymphoid tissues. The increase in peripheral infection led to early CNS seeding since infectious WNV was detected several days earlier in the brains and spinal cords of IFN-γ-/- or IFN-γR -/- mice. Bone marrow reconstitution experiments showed that γδ T cells require IFN-γ to limit dissemination by WNV. Moreover, treatment of primary dendritic cells with IFN-γ reduced WNV production by 130-fold. Collectively, our experiments suggest that the dominant protective role of IFN-γ against WNV is antiviral in nature, occurs in peripheral lymphoid tissues, and prevents viral dissemination to the CNS.

Original languageEnglish (US)
Pages (from-to)5338-5348
Number of pages11
JournalJournal of virology
Volume80
Issue number11
DOIs
StatePublished - Jun 1 2006

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Shrestha, B., Wang, T., Samuel, M. A., Whitby, K., Craft, J., Fikrig, E., & Diamond, M. S. (2006). Gamma interferon plays a crucial early antiviral role in protection against West Nile virus infection. Journal of virology, 80(11), 5338-5348. https://doi.org/10.1128/JVI.00274-06