The interferon-inducible gene viperin restricts West Nile virus pathogenesis

Kristy J. Szretter, James D. Brien, Larissa B. Thackray, Herbert W. Virgin, Peter Cresswell, Michael S. Diamond

Research output: Contribution to journalArticlepeer-review

122 Scopus citations

Abstract

Type I interferon (IFN) signaling coordinates an early antiviral program in infected and uninfected cells by inducing IFN-stimulated genes (ISGs) that modulate viral entry, replication, and assembly. However, the specific antiviral functions in vivo of most ISGs remain unknown. Here, we examined the contribution of the ISG viperin to the control of West Nile virus (WNV) in genetically deficient cells and mice. While modest increases in levels of WNV replication were observed for primary viperin -/- macrophages and dendritic cells, no appreciable differences were detected in deficient embryonic cortical neurons or fibroblasts. In comparison, viperin -/- adult mice infected with WNV via the subcutaneous or intracranial route showed increased lethality and/or enhanced viral replication in central nervous system (CNS) tissues. In the CNS, viperin expression was induced in both WNV-infected and adjacent uninfected cells, including activated leukocytes at the site of infection. Our experiments suggest that viperin restricts the infection of WNV in a tissue- and cell-type-specific manner and may be an important ISG for controlling viral infections that cause CNS disease.

Original languageEnglish
Pages (from-to)11557-11566
Number of pages10
JournalJournal of Virology
Volume85
Issue number22
DOIs
StatePublished - Nov 2011

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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