Murine norovirus 1 (MNV-1) is a newly recognized pathogen of mice that causes lethal infection in mice deficient in components of the innate immune response but not in wild-type 129 mice. In this study, in vitro-propagated MNV-1 was used as antigen to develop a multiplexed fluorescent immunoassay (MFI) to detect antibodies to MNV-1 in infected mice. The MNV-1 MFI was 100% specific and 100% sensitive in detecting anti-MNV-1 antibody in sera from experimentally infected mice. Testing of a large number of mouse serum samples (n ‫؍‬ 12,639) submitted from contemporary laboratory mouse colonies in the United States and Canada revealed that 22.1% of these sera contained antibodies to MNV-1, indicating infection with MNV-1 is widespread in research mice. In addition, a reverse transcriptase PCR primer pair with a sensitivity of 25 virus copies was developed and used to demonstrate that MNV-1 RNA could be detected in the spleen, mesenteric lymph node, and jejunum from some experimentally infected mice 5 weeks postinoculation. These diagnostic assays provide the necessary tools to define the MNV-1 infection status of research mice and to aid in the establishment of laboratory mouse colonies free of MNV-1 infection.

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.

Murine noroviruses (MNV) comprise a group of newly recognized pathogens infecting laboratory mice. The first reported murine norovirus, murine norovirus 1 (MNV-1), produces a transient infection with a short duration of fecal shedding after infection of immunocompetent laboratory mice. Our laboratory subsequently isolated three novel murine noroviruses, murine norovirus 2 (MNV-2), murine norovirus 3 (MNV-3), and murine norovirus 4 (MNV-4), that have markedly different pathogenicity from MNV-1 by producing persistent infections and prolonged fecal shedding in infected immunocompetent mice. In this study, the nucleotide sequences and the predicted amino acid sequences of the three novel murine noroviruses were determined and compared to each other, MNV-1, and other previously described human and animal noroviruses. The three novel murine norovirus strains were shown to be related to each other and MNV-1 by sequence and phylogenetic analysis even though MNV-2, MNV-3 and MNV-4 all display markedly different biologic behavior from that of MNV-1.