Inhibition of miR-93 promotes interferon effector signaling to suppress influenza A infection by upregulating JAK1.

• miR-93 was downregulated upon IAV infection in alveolar epithelial type 2. • miR-93 inhibited the antiviral function of type I IFN by targeting JAK1. • miR-93 downregulation promotes antiviral response by strengthening IFN cascade. • Antagomir-93 inhibits IAV replication in vivo, prevents 75% death of infected mice. Type I interferons play a critical role in host defense against influenza virus infection. Interferon cascade induces the expression of interferon-stimulated genes then subsequently promotes antiviral immune responses. The microRNAs are important regulators of innate immunity, but microRNAs-mediated regulation of interferon cascade during influenza infection remains to be fully identified. Here we found influenza A virus (IAV) infection significantly inhibited miR-93 expression in alveolar epithelial type II cells through RIG-I/JNK pathway. IAV-induced downregulation of miR-93 was found to upregulate JAK1, the target of miR-93, and then feedback promote antiviral innate response by facilitating IFN effector signaling. Importantly, in vivo administration of miR-93 antagomiR markedly suppressed IAV infection, protecting mice form IAVs -associated death. Hence, the inducible downregulation of miR-93 feedback suppress IAV infection by strengthening IFN-JAK-STAT pathway via JAK1 upregulation, and in vivo inhibition of miR-93 bears considerable therapeutic potential for suppressing IAV infection. [ABSTRACT FROM AUTHOR]