College of Medicine, Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL, USA.
Virology. 2011 Dec 20;421(2):202-10. doi: 10.1016/j.virol.2011.09.030. Epub 2011 Oct 22.
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.
人类诺如病毒是重要的新兴病原体，导致了全球大多数非细菌性胃肠炎爆发。最近发现的 30 种鼠诺如病毒株开始促进对诺如病毒发病机制的详细研究。在这里，我们对两种鼠诺如病毒株 MNV-1 和 MNV-3 进行了体内比较分析。在免疫功能正常的小鼠中，MNV-1 引起适度的肠道病理学，而 MNV-3 与 MNV-1 相比则减弱。然而令人惊讶的是，MNV-3 在肠道组织中的滴度高于 MNV-1。MNV-3 在缺乏关键干扰素信号分子 STAT-1 的小鼠中也显示出衰减，表明 MNV-3 的衰减不是由于干扰素敏感性增加所致。重要的是，感染 MNV-3 的小鼠在 STAT1(-/-)小鼠中体重减轻，并出现胃胀和腹泻，所有动物均从中恢复。这种疾病特征再现了感染人类诺如病毒的人所经历的急性胃肠炎的几个关键特征。
