Comparative Murine Norovirus Studies Reveal a Lack of Correlation Between Intestinal Virus Titers and Enteric Pathology

Virology. 2011 Dec 20;421(2):202-10. doi: 10.1016/j.virol.2011.09.030. Epub 2011 Oct 22.

Abstract

Human noroviruses are significant emerging pathogens, causing the majority of non-bacterial gastroenteritis outbreaks worldwide. The recent discovery of 30 murine norovirus strains is beginning to facilitate a detailed investigation of norovirus pathogenesis. Here, we have performed an in vivo comparative analysis of two murine norovirus strains, MNV-1 and MNV-3. In immunocompetent mice, MNV-1 caused modest intestinal pathology whereas MNV-3 was attenuated compared to MNV-1. Surprisingly though, MNV-3 reached higher titers in intestinal tissue than MNV-1. MNV-3 also displayed attenuation in mice deficient in the critical interferon signaling molecule STAT-1, demonstrating that MNV-3 attenuation is not a result of increased interferon sensitivity. Importantly, MNV-3-infected mice lost weight and developed gastric bloating and diarrhea in STAT1(-/-) mice, from which all animals recovered. This disease profile recapitulates several key features of acute gastroenteritis experienced by people infected with a human norovirus.

Publication types

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

MeSH terms

  • Animals
  • Caliciviridae Infections / immunology
  • Caliciviridae Infections / pathology*
  • Caliciviridae Infections / virology*
  • Cell Line
  • Gastroenteritis / immunology
  • Gastroenteritis / pathology
  • Gastroenteritis / virology*
  • Interferons / immunology
  • Mice
  • Mice, Inbred C3H
  • Mice, Knockout
  • Norovirus / growth & development
  • Norovirus / immunology
  • Norovirus / pathogenicity*
  • STAT1 Transcription Factor / deficiency
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / metabolism
  • Viral Load*
  • Virus Replication

Substances

  • STAT1 Transcription Factor
  • Stat1 protein, mouse
  • Interferons