Intestinal epithelia activate anti-viral signaling via intracellular sensing of rotavirus structural components

Rotavirus (RV), a leading cause of severe diarrhea, primarily infects intestinal epithelial cells (IEC) causing self-limiting illness. In order to better understand innate immunity to RV, we sought to define the extent to which IEC activation of anti-viral responses required viral replication or could be recapitulated by inactivated RV or its components. Using model human intestinal epithelia, we observed that RV-induced activation of signaling events and gene expression typically associated with viral infection was largely mimicked by administration of UV-inactivated RV. Use of anti-IFN neutralizing antibodies revealed that such replication-independent anti-viral gene expression required type I interferon signaling. In contrast, RV-induction of NF-κB-mediated IL-8 expression was dependent upon viral replication. The anti-viral gene expression induced by UV-RV was not significantly recapitulated by RV RNA or RV VLP even though the latter could enter IEC. Together, these results suggest that RV proteins mediate viral entry into epithelial cells leading to intracellular detection of RV RNA that generates an anti-viral response.