Commensal microbes and interferon-λ determine persistence of enteric murine norovirus infection

Science. 2015 Jan 16;347(6219):266-9. doi: 10.1126/science.1258025. Epub 2014 Nov 27.

Abstract

The capacity of human norovirus (NoV), which causes >90% of global epidemic nonbacterial gastroenteritis, to infect a subset of people persistently may contribute to its spread. How such enteric viruses establish persistent infections is not well understood. We found that antibiotics prevented persistent murine norovirus (MNoV) infection, an effect that was reversed by replenishment of the bacterial microbiota. Antibiotics did not prevent tissue infection or affect systemic viral replication but acted specifically in the intestine. The receptor for the antiviral cytokine interferon-λ, Ifnlr1, as well as the transcription factors Stat1 and Irf3, were required for antibiotics to prevent viral persistence. Thus, the bacterial microbiome fosters enteric viral persistence in a manner counteracted by specific components of the innate immune system.

Publication types

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

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Caliciviridae Infections / drug therapy
  • Caliciviridae Infections / immunology
  • Caliciviridae Infections / microbiology
  • Caliciviridae Infections / virology*
  • Cytokines / physiology*
  • Female
  • Gastroenteritis / drug therapy
  • Gastroenteritis / immunology
  • Gastroenteritis / microbiology
  • Gastroenteritis / virology*
  • Intestines / microbiology*
  • Intestines / virology
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microbiota* / drug effects
  • Norovirus / immunology
  • Norovirus / physiology*
  • Receptors, Cytokine / genetics
  • Receptors, Cytokine / metabolism
  • Signal Transduction
  • Symbiosis*
  • Viral Load
  • Virus Replication
  • Virus Shedding

Substances

  • Anti-Bacterial Agents
  • Cytokines
  • Receptors, Cytokine
  • interferon-lambda protein, mouse

Associated data

  • BioProject/PRJEB7745