Cell Host & Microbe
Volume 24, Issue 5, 14 November 2018, Pages 677-688.e5
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Article
Murine Norovirus Infection Induces TH1 Inflammatory Responses to Dietary Antigens

https://doi.org/10.1016/j.chom.2018.10.004Get rights and content
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Highlights

  • Murine norovirus strain CW3, but not CR6, promotes TH1 immunity to dietary antigens

  • Capsid protein of CW3 is crucial to trigger IRF1-dependent loss of oral tolerance

  • Transcriptional analysis reveals immunopathology and protective immunity are separable

  • A common virus-induced transcriptional signature is found for loss of oral tolerance

Summary

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.

Keywords

celiac disease
norovirus
reovirus
T helper 1
TH1
major capsid protein
oral tolerance
inflammation
interferon regulatory factor 1
IRF1

Cited by (0)

11

These authors contributed equally

12

Present address: Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

13

Lead Contact