Rotaviral components induce a type 1 IFN response via an apical receptor in intestinal epithelia

Abstract

Rotaviruses (RV) are the leading cause of diarrhea in children. RV primarily infects intestinal epithelial cells, which typically clear the infection within 7 days via pathways not strictly dependent on adaptive immunity. We hypothesize such innate immune clearance of RV is mediated by epithelial antiviral gene expression involving type 1 interferon (IFN), and that these antiviral responses are induced upon detection of RV components. Thus, we sought to define anti‐viral signaling induced in epithelia by RV infection and determine the extent to which this response was recapitulated by non‐infectious RV components. Model human intestinal epithelia (HT29 cells grown on permeable supports) were treated with RV (MOI 1‐3) or UV‐irradiated RV (UV‐RV) which was non‐infectious but structurally intact. Viral protein expression and activation of antiviral markers such as IRF (3/7), STAT1, and PKR was detected by western blotting. Type 1 IFN‐α / β and IL‐8 (inflammatory cytokine) induction was measured by qRT‐PCR or ELISA. Apical, but not basolateral, treatment of model epithelia with RV resulted in productive infection and robust activation of these pathways including IFN‐ β but not IFN‐α. This pattern of anti‐viral signaling was largely mimicked by UV‐RV. Our results suggest intestinal epithelia detect rotaviral components via an apical receptor and mount type 1 IFN responses as part of a cellular antiviral program.