Effect of all-trans-retinoic acid on enterovirus 71 infection in vitro

Our previous studies have shown that vitamin A (VA) status is associated with antiviral immunity and pathogenic conditions in enterovirus 71 (EV71)-infected children. In the present study, we established an in vitro model to investigate the effects and potential mechanism of the antiviral activity of VA. Human monocytic U937 cells were cultured in vitro and infected with EV71. All-trans-retinoic acid (ATRA), the active metabolite of VA, and Ro 41-5253, a retinoic acid receptor-α (RAR-α) antagonist, were used as the experimental treatment agents. The percentage of EV71-infected cells and apoptosis induced by EV71 were determined using flow cytometry. The level of interferon-α (IFN-α) in the supernatants of the cultures was detected using ELISA. The expression of retinoid-induced gene I (RIG-I) and its downstream genes was examined with real-time quantitative PCR. The results indicated that ATRA reduced the percentage of EV71-infected cells and protected cells against EV71-induced apoptosis. Correspondingly, ATRA increased the production of IFN-α one of the most important antiviral cytokines, at both mRNA and protein levels in EV71-infected cells. In addition, the expression of RIG-I mRNA and its downstream genes was up-regulated by ATRA in EV71-infected cells. Ro 41-5253 abrogated the inhibitory effects of ATRA on EV71. The present findings suggest that ATRA is an interferon-inducing agent with antiviral activity against EV71 in vitro and that its actions are mediated at least in part by RAR-α activity and the RIG-I signalling pathway.