Axin1: A novel scaffold protein joins the antiviral network of interferon

Acute respiratory infection by influenza virus is a persistent and pervasive public health problem. Antiviral innate immunity initiated by type I interferon (IFN) is the first responder to pathogen invasion and provides the first line of defense. We discovered that Axin1, a scaffold protein, was reduced during influenza virus infection. We also found that overexpression of Axin1 and the chemical stabilizer of Axin1, XAV939, reduced influenza virus replication in lung epithelial cells. This effect was also observed with respiratory syncytial virus and vesicular stomatitis virus. Axin1 boosted type I IFN response to influenza virus infection and activated JNK/c-Jun and Smad3 signaling. XAV939 protected mice from influenza virus infection. Thus, our studies provide new mechanistic insights into the regulation of the type I IFN response and present a new potential therapeutic of targeting Axin1 against influenza virus infection.

Automated summary

Influenza virus infection leads to reduced levels of Axin1, while overexpression of Axin1 and the chemical stabilizer XAV939 can inhibit virus replication and enhance the type I interferon response. Axin1 also activates JNK/c-Jun and Smad3 signaling pathways. XAV939 protects mice from influenza virus infection. These findings provide new insights into the regulation of the type I interferon response and suggest Axin1 as a potential therapeutic target against influenza virus infection.