Inhibition of miR-93 Promotes Interferon Effector Signaling to Suppress Influenza A Infection by Upregulating JAK1

Type I interferon (IFN) plays critical roles in host antiviral innate immune response, and regulation of IFN effector signaling has attracted much attention. microRNAs are important regulators of innate immune response, but microRNAs regulated IFN effector signaling still need further investigation. Here, during influenza A virus (IAV) infection, we found that miR-93 expression was significantly downregulated in Alveolar epithelial type II cells (AT2) upon IAVs infection through RIG-I/JNK pathway. Inhibition of miR-93 was found to promote host antiviral innate response by facilitating type I IFN effector signaling, and JAK1 was identified to be directly targeted by miR-93. Importantly, in vivo administration of miR-93 antagomiR significantly inhibited miR-93 expression and markedly suppressed IAVs infection, which in turn prevented the death of IAVs infected mice. Hence, the inducible downregulation of miR-93 suppress IAVs infection by upregulation IFN-JAK-STAT effector pathway, and in vivo inhibition of miR-93 bears considerable therapeutic potential for suppressing IAVs infection.