miR‐127‐5p negatively regulates enterovirus 71 replication by directly targeting SCARB2

Enterovirus 71 (EV71) is the major causative agent of hand‐foot‐and‐mouth disease in young children and can cause severe cerebral and pulmonary complications and even fatality. This study aimed at elucidating whether and how EV71 infection is regulated by a cellular microRNA, miR‐127‐5p. We found that miR‐127‐5p can downregulate the expression of SCARB2, a main receptor of EV71, by targeting two potential sites in its 3′ UTR region and inhibit EV71 infection. Meanwhile, miR‐127‐5p expression was upregulated during EV71 infection. Notably, transfecting cells with miR‐127‐5p mimics led to a significant decrease in viral replication, while inhibition of endogenous miR‐127‐5p facilitated viral replication. Furthermore, our evidence showed that miR‐127‐5p did not affect postentry viral replication. Taken together, these results indicated that miR‐127‐5p inhibited EV71 replication by targeting the SCARB2 mRNA. Enterovirus 71 (EV71) is the major causative agent of hand‐foot‐and‐mouth disease. The potential regulatory target of miR‐127‐5p is SCARB2, a cell surface protein known to be the receptor of EV71. Here, we demonstrated that miR‐127‐5p inhibited EV71 entry into cells and reduced viral replication by targeting the 3′ UTR of SCARB2 mRNA. miR‐127‐5p was upregulated during viral infection, possibly as a result of the host defense mechanism.