Comparative murine norovirus studies reveal a lack of correlation between intestinal virus titers and enteric pathology.
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.
College of Medicine, Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL, USA.
Shannon M
SM
Kahan
Guangliang
G
Liu
Mary K
MK
Reinhard
Charlie C
CC
Hsu
Robert S
RS
Livingston
Stephanie M
SM
Karst
D000818:Animals; D017250:Caliciviridae Infections / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D002460:Cell Line; D005759:Gastroenteritis / Q000276:immunology / Q000473:pathology / Q000821:virology*; D007372:Interferons / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D029322:Norovirus / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity*; D050794:STAT1 Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D019562:Viral Load; D014779:Virus Replication
D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D007372:Interferons