An enteric virus can replace the beneficial function of commensal bacteria

Nature. 2014 Dec 4;516(7529):94-8. doi: 10.1038/nature13960. Epub 2014 Nov 19.


Intestinal microbial communities have profound effects on host physiology. Whereas the symbiotic contribution of commensal bacteria is well established, the role of eukaryotic viruses that are present in the gastrointestinal tract under homeostatic conditions is undefined. Here we demonstrate that a common enteric RNA virus can replace the beneficial function of commensal bacteria in the intestine. Murine norovirus (MNV) infection of germ-free or antibiotic-treated mice restored intestinal morphology and lymphocyte function without inducing overt inflammation and disease. The presence of MNV also suppressed an expansion of group 2 innate lymphoid cells observed in the absence of bacteria, and induced transcriptional changes in the intestine associated with immune development and type I interferon (IFN) signalling. Consistent with this observation, the IFN-α receptor was essential for the ability of MNV to compensate for bacterial depletion. Importantly, MNV infection offset the deleterious effect of treatment with antibiotics in models of intestinal injury and pathogenic bacterial infection. These data indicate that eukaryotic viruses have the capacity to support intestinal homeostasis and shape mucosal immunity, similarly to commensal bacteria.

Publication types

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

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Physiological Phenomena / immunology*
  • Citrobacter rodentium / physiology
  • Enterobacteriaceae Infections / immunology
  • Enterovirus / immunology
  • Enterovirus / physiology*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation / immunology
  • Immunity, Innate / immunology
  • Immunity, Mucosal / immunology*
  • Interferon Type I / immunology
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / virology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Norovirus / immunology
  • Norovirus / physiology
  • Signal Transduction / immunology
  • Specific Pathogen-Free Organisms


  • Anti-Bacterial Agents
  • Interferon Type I

Associated data

  • GENBANK/KM463105
  • GEO/GSE60163