Rotaviruses and their components induce antiviral gene expression in intestinal epithelia

Rotavirus, the world's leading cause of severe diarrhea in children, primarily infects the epithelial cells of the small intestine. Rotavirus is typically cleared within 7 days via pathways not strictly dependent on adaptive immunity. Therefore, we hypothesize that epithelial cell antiviral gene expression is important for host defense against rotavirus and sought to define the mechanism by which epithelia detect rotavirus, particularly whether epithelial antiviral gene expression resulted from detection of a viral component or required active viral replication. Polarized model intestinal epithelia were treated with live rhesus rotavirus (RRV) (MOI 1–3) or RRV that had been UV‐irradiated (UV‐RRV) to render it non‐infectious but leave its epitopes intact. Expression of viral proteins and activation of interferon regulatory factors 3 and 7 (IRF 3/7) and STAT 1/3 were measured by western blotting. Cytokines IL‐8 and IFNB were measured by ELISA. Apical, but not basolateral, treatment of model epithelia with RRV resulted in productive infection (synthesis of viral proteins) and robust activation of all pathways measured. Interestingly, such activation of host antiviral pathways was largely recapitulated by treatment with UV‐RRV. Together, these results suggest that epithelial antiviral gene expression may result from activation of an apical receptor that detects a component of rotavirus.