The Role of Interferon in Persistent Viral Infection: Insights from Murine Norovirus

Timothy Nice, Bridget A. Robinson, Jacob A. Van Winkle

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Persistent viral infections result from evasion or avoidance of sterilizing immunity, extend the timeframe of virus transmission, and can trigger disease. Prior studies in mouse models of persistent infection have suggested that ineffective adaptive immune responses are necessary for persistent viral infection. However, recent work in the murine norovirus (MNV) model of persistent infection demonstrates that innate immunity can control both early and persistent viral replication independently of adaptive immune effector functions. Interferons (IFNs) are central to the innate control of persistent MNV, apart from a role in modulating adaptive immunity. Furthermore, subtypes of IFN play distinct tissue-specific roles in innate control of persistent MNV infection. Type I IFN (IFN-α/β) controls systemic replication, and type III IFN (IFN-λ) controls MNV persistence in the intestinal epithelium. In this article, we review recent findings in the MNV model, highlighting the role of IFNs and innate immunity in clearing persistent viral infection, and discussing the broader implications of these findings for control of persistent human infections. The MNV model system is ideal for studying virus and host determinants of persistence in the intestine.MNV nonstructural protein NS1 determines tropism for intestinal epithelial cells (IECs) and persistent viral shedding.IFN-λ and IFN-α/β are primary host determinants of MNV persistence, and have tissue-specific roles.A sterilizing cell-intrinsic IFN-λ response in IECs is necessary for MNV clearance from the intestine, independently of adaptive immunity.A sterilizing cell-intrinsic IFN-α/β response in myeloid cells in necessary for systemic MNV clearance in conjunction with adaptive immunity.IFN-λ and epithelial cells play a general role in clearance of viral infections from barrier tissues.

Original languageEnglish (US)
JournalTrends in Microbiology
DOIs
StateAccepted/In press - Jan 1 2017

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)
  • Infectious Diseases
  • Virology

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