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

作者：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 · 发表于：Science Signaling · 年份：2020 · DOI：10.1126/scisignal.aaz3381 · 被引用次数：28 · 研究领域：interferon and immune responses、Influenza Virus Research Studies、Cytokine Signaling Pathways and Interactions

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 influenza A virus.