MicroR-9-5p Suppresses EV71 Replication Through Targeting NFκB of the RIG-I-mediated Innate Immune Response
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Accumulating evidence demonstrates that there is a causative link between hsa-microRNA-9-5p (miR-9) and pathophysiological processes. Enterovirus 71 (EV71) has been found to contribute to numerous severe clinical symptoms which result in death. The exact mechanism by which EV71 influences miR-9 expression is unknown, and the relationship between miR-9 and EV71 is still unclear. Here, miR-9 expression was found to be impaired upon EV71 infection in several cell lines and in an EV71 infection mouse model. Additionally, we confirmed that EV71 infection induces robust expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1) and interferons (IFN-α and IFN-β). Overexpression of miR-9 attenuated EV71 proliferation and reduced protein and gene expressions of virion protein 1 (VP1) of EV71. Furthermore, we observed that the inflammation caused by EV71 infection was restored to a moderate level via miR-9 overexpression. Nuclear factor kappa B (NFκB) in the retinoic acid-induced gene 1 (RIG-I) signaling pathway, but not interferon regulating factor 3 (IRF3), was significantly decreased and inactivated by ectopic miR-9 expression. Moreover, in mouse infection experiments, administration of miR-9 agomirs caused a significant decrease in VP1 levels and pro-inflammatory cytokine production after viral inoculation. Taken together, the present data demonstrate that miR-9 exerts an anti-EV71 effect in cells and a mouse model via mediating NFκB activity of the RIG-I signal pathway, thereby suggesting a new candidate for antiviral drug development.
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