Inducible downregulation of miR-93 feedback promotes innate responses against RNA virus by amplifying interferon signaling

Type I interferons (IFN) and their downstream effector signaling pathways play critical roles in the innate antiviral response. The underlying mechanisms that regulate IFN production and their effector signaling, especially by microRNAs, are well understood. We found that the expression of miR-93 was significantly downregulated by RNA virus infection in innate cells. miR-93 expression was also downregulated in influenza virus-infected patients. Furthermore, we showed that JAK1 is targeted by miR-93 to inhibit type I IFN's antiviral activity. Functionally, an-tagomir of miR-93 markedly reduced influenza virus replication in mice in vivo and prevented their death. Therefore, hosts recognize the invading RNA virus infection and activate RIG-I/JNK pathways to decrease miR-93 expression. The reduction of miR-93 feedback enhances the antiviral innate immune response by activating the IFN-JAK-STAT effectors type I, indicating miR-93 as a possible therapeutic target for infection with RNA viruses.

Automated summary

It has been found that the expression of miR-93 is significantly downregulated in innate cells and in patients infected with RNA viruses, including influenza virus. It has been shown that miR-93 inhibits the antiviral activity of type I interferons by targeting JAK1. Antagomirs of miR-93 can reduce influenza virus replication and prevent death in mice, suggesting miR-93 as a potential therapeutic target for RNA virus infection.