A Single Mutation in an Enteric Virus Alters Tropism and Sensitivity to Microbiota

Abstract

Many enteric viruses benefit from the microbiota, and depletion of the microbiota reduces infection of noroviruses and picornaviruses in mice. However, Reovirales viruses are outliers among enteric viruses. Rotavirus infection is inhibited by bacteria, and we determined that several reovirus strains have enhanced replication following microbiota depletion. We found that an isogenic pair of reoviruses have opposing infection outcomes after microbiota depletion. Microbiota depletion reduces infection of reovirus strain T3SA+ but increases infection of strain T3SA-. These strains differ by a single amino acid polymorphism in the {sigma}1 attachment protein, which confers sialic acid binding to T3SA+. Sialic acid binding facilitates T3SA+ infection of intestinal endothelial cells, while T3SA- inefficiently infects intestinal epithelial cells due to restriction by microbiota-driven, host-derived type III interferon responses. This study enhances an understanding of the complex interactions of enteric viruses, the microbiota, intestinal tropism, and antiviral responses. HighlightsO_LIMicrobiota enhance infection of a sialic acid (SA)-binding reovirus strain but inhibit infection of an isogenic non-SA-binding reovirus strain that differs by a single amino acid change. C_LIO_LISA binding facilitates viral infection of intestinal endothelial cells in a microbiota-dependent manner. C_LIO_LIA non-SA-binding reovirus strain inefficiently infects intestinal epithelial cells due to microbiota-driven type III interferon responses. C_LI