Identification of a novel cellular target and a co-factor for norovirus infection – B cells & commensal bacteria

Abstract

Human noroviruses are a leading cause of gastroenteritis worldwide but research on these important enteric pathogens has long been restricted by their uncultivability. Extensive efforts to infect intestinal epithelial cells with murine and human noroviruses in vitro have been thus far unsuccessful while murine noroviruses efficiently and lytically infect innate immune cells including macrophages and dendritic cells. We have recently discovered that murine and human noroviruses infect B cells in vitro. The nature of B cell infection was distinct from innate immune cell infection in that mature B cells were infected noncytopathically in contrast to the lytic infection of macrophages and dendritic cells. Human norovirus infection of B cells was facilitated by commensal bacteria expressing an appropriate histo-blood group antigen. Importantly, we used the mouse model of norovirus infection to confirm that Peyer's patch B cells are infected, and that commensal bacteria stimulate infection, in vivo.