IFN- κ suppresses the replication of influenza A viruses through the IFNAR-MAPK-Fos-CHD6 axis.

IFN-κ suppresses the replication of influenza A viruses through the IFNAR-MAPK-Fos-CHD6 axis. Sci Signal. 2020 Apr 07;13(626): Authors: He Y, Fu W, Cao K, He Q, Ding X, Chen J, Zhu L, Chen T, Ding L, Yang Y, Zhu C, Yuan S, Li Z, Zhao C, Zhang X, Xu J Abstract Type I interferons (IFNs) are the first line of defense against viral infection. Using a mouse model of influenza A virus infection, we found that IFN-κ was one of the earliest responding type I IFNs after infection with H9N2, a low-pathogenic avian influenza A virus, whereas this early induction did not occur upon infection with the epidemic-causing H7N9 virus. IFN-κ efficiently suppressed the replication of various influenza viruses in cultured human lung cells, and chromodomain helicase DNA binding protein 6 (CHD6) was the major effector for the antiviral activity of IFN-κ, but not for that of IFN-α or IFN-β. The induction of CHD6 required both of the type I IFN receptor subunits IFNAR1 and IFNAR2, the mitogen-activated protein kinase (MAPK) p38, and the transcription factor c-Fos but was independent of signal transducer and activator of transcription 1 (STAT1) activity. In addition, we showed that pretreatment with IFN-κ protected mice from lethal influenza viral challenge. Together, our findings identify an IFN-κ-specific pathway that constrains influenza A virus and provide evidence that IFN-κ may have potential as a preventative and therapeutic agent against infl...
Source: Science Signaling - Category: Biomedical Science Authors: Tags: Sci Signal Source Type: research