Journal
VIROLOGY
Volume 421, Issue 2, Pages 202-210Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2011.09.030
Keywords
Norovirus; Viral pathogenesis; Gastroenteritis; Viral attenuation
Categories
Funding
- NIH [AI081921, AI082310]
- NIH COBRE Center for Molecular and Tumor Virology [P20-RR018724]
- Louisiana Board of Regents [LEQSF(2008-11)-RD-A-16]
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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. (C) 2011 Elsevier Inc. All rights reserved.
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