Viral complementation of immunodeficiency confers protection against enteric pathogens via interferon-λ

Nat Microbiol. 2019 Jul;4(7):1120-1128. doi: 10.1038/s41564-019-0416-7. Epub 2019 Apr 1.

Abstract

Commensal microbes profoundly impact host immunity to enteric viral infections1. We have shown that the bacterial microbiota and host antiviral cytokine interferon-λ (IFN-λ) determine the persistence of murine norovirus in the gut2,3. However, the effects of the virome in modulating enteric infections remain unexplored. Here, we report that murine astrovirus can complement primary immunodeficiency to protect against murine norovirus and rotavirus infections. Protection against infection was horizontally transferable between immunocompromised mouse strains by co-housing and fecal transplantation. Furthermore, protection against enteric pathogens corresponded with the presence of a specific strain of murine astrovirus in the gut, and this complementation of immunodeficiency required IFN-λ signalling in gut epithelial cells. Our study demonstrates that elements of the virome can protect against enteric pathogens in an immunodeficient host.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astroviridae / classification
  • Astroviridae / genetics
  • Astroviridae / isolation & purification
  • Astroviridae / physiology
  • Caliciviridae Infections / immunology
  • Caliciviridae Infections / prevention & control*
  • Caliciviridae Infections / virology
  • Fecal Microbiota Transplantation
  • Feces / virology
  • Female
  • Gastroenteritis / immunology
  • Gastroenteritis / prevention & control*
  • Gastroenteritis / virology
  • Gastrointestinal Tract / metabolism
  • Gastrointestinal Tract / virology*
  • Immunocompromised Host*
  • Interferons / metabolism*
  • Intestinal Mucosa / metabolism
  • Male
  • Mice
  • Norovirus / immunology*
  • Signal Transduction
  • Virus Shedding

Substances

  • Interferons