Enterovirus 71-induced has-miR-21 contributes to evasion of host immune system by targeting MyD88 and IRAK1

•miR-21 expression was upregulated by EV71 infection.•Overexpression of miR-21 enhanced EV71 replication while miR-21 inhibition led to significant alleviation of viral replication.•miR-21 facilitates EV71 replication by counteracting antiviral activity of IFN-β.•miR-21 regulates IFN signaling through suppression of endogenous MyD88 and IRAK1, thereby inhibiting type I IFN production.

Enterovirus71(EV71), the etiological agent of hand-foot-and-mouth disease, has increasingly become a public health challenge around the world. Type I interferons (IFNs) are an important family of cytokines that regulate innate and adaptive immune responses to pathogens.These pathways are tightly regulated by the host to prevent an inappropriate cellular response, but viruses can modulate these pathways to proliferate and spread. In this study, we demonstrated that EV71 evades the immune surveillance system to proliferate by activating microRNA-21. We demonstrated that EV71 infection upregulates miR-21, which in turn suppresses EV71-triggered type I IFN production, thus promoting EV71 replication. Furthermore, we demonstrated that miR-21 targets the myeloid differentiation factor 88(MyD88) and interleukin-1 receptor-associated kinase 1(IRAK1), which are involved in EV71-induced type I IFN production.