Robust Antiviral Responses To Enterovirus 71 Infection In Human Intestinal Epithelial Cells

Enterovirus 71 (EV71) is a single-stranded RNA virus that belongs to Picornaviridae family. It causes the hand-foot-and-mouth disease and fatal neurological diseases in young children and infants. The mechanism of EV71 pathogenesis remains obscure. The intestinal tract is the initial site of EV71 replication, but no or only mild symptoms are observed in gastrointestinal system, suggesting that host immune responses of the intestinal epithelium to EV71 may be unique, which, however, has been rarely investigated. In this study, we showed that human intestinal epithelial cells HT-29 were susceptible to EV71, and the infected cells exhibited cytopathic effects (CPEs) and were prone to apoptosis. TLR-7 and TLR-8 were induced significantly post infection and may be pivotal in the induction of IFN-β and host innate immune response against EV71.Among proinflammatory responses in EV7-infected intestinal epithelial cells, IL-6, CCL5,and IP 10 were up-regulated and may play a major role in intestinal pathogenicity. We examined that both death receptor-mediated extrinsic and mitochondria-mediated intrinsic apoptotic pathways which were both activated in EV71, the mitochondria-mediated pathway may also be activated through caspase8-cleved tBid. Robust induction of IFNp in human intestinal epithelial cells contradicts that the finding that IFN induction was suppressed in other types of the cells indicating that a mild gastrointestinal system symptoms may be the result of sufficient local antiviral inductions. Systemic spread of the virus causing CNS symptoms may be caused by failed IFN induction. Our study has demonstrated a unique way of antiviral responses in human gut different from other tissue cells in response to EV71, which may account for mild symptom in intestinal tract. This finding will broaden our understanding of host defense mechanism and the pathogenesis of EV71 infection.