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

• DOI: 10.1126/scisignal.aaz3381
• Publication Date: 2020-04-07T23:10:55Z
• Authors: Yongquan He; Weihui Fu; Kangli Cao; Qian He; Xiangqing Ding; Jian Chen; Lingyan Zhu; Tianyue Chen; Longfei Ding; Yu Yang; Cuisong Zhu; Songhua Yuan; Zejun Li; Chen Zhao; Xiaoyan Zhang; Jianqing Xu
• Keywords: STAT1; IRF7

Type I interferons (IFNs) are the first line of defense against viral infection. Using a mouse model influenza A virus infection, we found that IFN-κ was one earliest responding type IFNs after infection with H9N2, low-pathogenic avian virus, whereas this early induction did not occur upon epidemic-causing H7N9 virus. efficiently suppressed replication various viruses in cultured human lung cells, and chromodomain helicase DNA binding protein 6 (CHD6) major effector for antiviral activity IFN-κ, but IFN-α or IFN-β. The CHD6 required both IFN receptor subunits IFNAR1 IFNAR2, mitogen-activated kinase (MAPK) p38, transcription factor c-Fos independent signal transducer activator 1 (STAT1) activity. In addition, showed pretreatment protected mice from lethal challenge. Together, our findings identify an IFN-κ-specific pathway constrains provide evidence may have potential as preventative therapeutic agent