The influence of intestinal microbiota on norovirus infections
All enteric viruses encounter intestinal microbiota as they traverse the intestinal tract so it is imperative to consider how virus-bacteria interactions impact the outcome of these infections. Indeed, commensal bacteria and the metabolites they produce influence infections of many mammalian viruses in both promoting and inhibitory manners, with mechanisms ranging from direct regulation to modulation of the host immune response. Using murine norovirus (MNV) as a model system, we discovered that a single class of bacterial metabolites – bile acids – play opposing regional roles in regulating an enteric virus infection. We are interested is understanding the regional nature of these phenotypes since this will provide fundamental insight into the maintenance of intestinal compartmentalization. This is especially intriguing considering the expanding appreciation of bile acids as key regulators of mucosal immune responses.
We have also discovered that intestinal microbiota protect neonatal hosts from severe norovirus infection. Considering that infants are susceptible to severe and even life-threatening norovirus disease outcomes, understanding how microbiota provide protection from disease could pave the way for developing new treatments. These studies should also provide general insight into the mechanisms by which neonatal colonization by commensal microorganisms shapes host susceptibility to pathogens and development of mucosal immunity.