Elsevier

Virology

Volume 421, Issue 2, 20 December 2011, Pages 202-210
Virology

Comparative murine norovirus studies reveal a lack of correlation between intestinal virus titers and enteric pathology

https://doi.org/10.1016/j.virol.2011.09.030Get rights and content
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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.

Keywords

Norovirus
Viral pathogenesis
Gastroenteritis
Viral attenuation

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1

Current address: Safety Assessment/Laboratory Animal Resources, Merck and Co., Inc, West Point, PA, USA.