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The intestinal regionalization of acute norovirus infection is regulated by the microbiota via bile acid-mediated priming of type III interferon.

Abstract：

:Evidence has accumulated to demonstrate that the intestinal microbiota enhances mammalian enteric virus infections1. For example, we and others previously reported that commensal bacteria stimulate acute and persistent murine norovirus infections2-4. However, in apparent contradiction of these results, the virulence of murine norovirus infection was unaffected by antibiotic treatment. This prompted us to perform a detailed investigation of murine norovirus infection in microbially deplete mice, revealing a more complex picture in which commensal bacteria inhibit viral infection of the proximal small intestine while simultaneously stimulating the infection of distal regions of the gut. Thus, commensal bacteria can regulate viral regionalization along the intestinal tract. We further show that the mechanism underlying bacteria-dependent inhibition of norovirus infection in the proximal gut involves bile acid priming of type III interferon. Finally, the regional effects of the microbiota on norovirus infection may result from distinct regional expression profiles of key bile acid receptors that regulate the type III interferon response. Overall, these findings reveal that the biotransformation of host metabolites by the intestinal microbiota directly and regionally impacts infection by a pathogenic enteric virus.

journal_name

Nat Microbiol

journal_title

Nature microbiology

authors

Grau KR,Zhu S,Peterson ST,Helm EW,Philip D,Phillips M,Hernandez A,Turula H,Frasse P,Graziano VR,Wilen CB,Wobus CE,Baldridge MT,Karst SM

doi

10.1038/s41564-019-0602-7

subject

Has Abstract

pub_date

2020-01-01 00:00:00

pages

84-92

issue

1

issn

2058-5276

pii

10.1038/s41564-019-0602-7

journal_volume

5

pub_type

杂志文章

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