Murine Norovirus Infection Induces TH1 Inflammatory Responses to Dietary Antigens

Romain Bouziat, Scott B. Biering, Elaine Kouame, Kishan A. Sangani, Soowon Kang, Jordan D. Ernest, Mukund Varma, Judy J. Brown, Kelly Urbanek, Terence S. Dermody, Aylwin Ng, Reinhard Hinterleitner, Seungmin Hwang, Bana Jabri

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

Intestinal reovirus infection can trigger T helper 1 (TH1) immunity to dietary antigen, raising the question of whether other viruses can have a similar impact. Here we show that the acute CW3 strain of murine norovirus, but not the persistent CR6 strain, induces TH1 immunity to dietary antigen. This property of CW3 is dependent on its major capsid protein, a virulence determinant. Transcriptional profiling of mesenteric lymph nodes following infection reveals an immunopathological signature that does not segregate with protective immunity but with loss of oral tolerance, in which interferon regulatory factor 1 is critical. These data show that viral capacity to trigger specific inflammatory pathways at sites where T cell responses to dietary antigens take place interferes with the development of tolerance to an oral antigen. Collectively, these data provide a foundation for the development of therapeutic strategies to prevent TH1-mediated complex immune disorders triggered by viral infections. Bouziat et al. discover that murine norovirus can induce loss of oral tolerance. Specifically, the CW3 strain triggers interferon regulatory factor 1-mediated induction of TH1 immunity via its major viral capsid protein. Transcriptional profiling reveals a common immunopathological signature in loss of oral tolerance, which can be dissociated from protective immunity.

Original languageEnglish
Pages (from-to)677-688.e5
JournalCell Host and Microbe
Volume24
Issue number5
DOIs
StatePublished - 14 Nov 2018
Externally publishedYes

Keywords

  • IRF1
  • T helper 1
  • T1
  • celiac disease
  • inflammation
  • interferon regulatory factor 1
  • major capsid protein
  • norovirus
  • oral tolerance
  • reovirus

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