Murine Norovirus: a Model System To Study Norovirus Biology and Pathogenesis

Abstract

Human noroviruses are the major cause of nonbacterial, epidemic gastroenteritis worldwide (19,23,33,46) and cause significant numbers of endemic cases, as well.One study from 1999 estimated that, in the United States alone, human noroviruses cause 23 million cases of gastroenteritis and 50,000 hospitalizations per year (49).Norovirus outbreaks involve people of all ages and often occur in crowded locations, such as cruise ships, aircraft carriers, nursing homes, hospitals, schools, and restaurants (23).Noroviruses are classified as class B biological agents due to their high infectivity and stability and to the suddenness of outbreaks and the debilitating nature of the disease.Despite the significant economic impact and considerable morbidity caused by human noroviruses, no drug or vaccine is currently available to treat or prevent human norovirus disease.In addition, many aspects of norovirus biology are not well understood.This is due in large part to the absence of a cell culture system or small animal model for human noroviruses (16,23).Although most noroviruses have been associated with gastrointestinal disease in humans, noroviruses of cattle, swine and mice have also been identified (36,44,70).Of these potential experimental models, the murine norovirus (MNV) is the only norovirus that replicates in cell culture and in a small animal (36,75).Moreover, laboratory mice are a versatile and relatively inexpensive model for the analysis of viral pathogenesis.A recent analysis of a large number of mouse serum samples from research colonies in the United States and Canada identified MNV-1 reactive antibodies in 22.1% of serum samples (30).In addition, over 35 new isolates of MNV have been found in research colonies (GenBank accession no.DQ223041 to DQ223043 and DQ269192 to DQ269205; unpublished observations).Therefore, MNV is one of the most prevalent pathogens in research mice today.Independent of its value as a potential model for norovirus infection, the impact of MNV infection on biomedical research, which is highly dependent on mice as experimental models, may be of great significance.The MNV model system provides the first opportunity to understand the relationship between basic mechanisms of norovirus replication in tissue culture and pathogenesis in a nat-