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.

中文翻译：

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IFN-κ 通过 IFNAR-MAPK-Fos-CHD6 轴抑制甲型流感病毒的复制。

I 型干扰素 (IFN) 是抵御病毒感染的第一道防线。使用甲型流感病毒感染的小鼠模型，我们发现 IFN-κ 是感染 H9N2（一种低致病性甲型流感病毒）后最早响应的 I 型干扰素之一，而这种早期诱导并未在感染 H9N2 后发生。引起流行的 H7N9 病毒。IFN-κ 有效抑制培养的人肺细胞中各种流感病毒的复制，染色质解旋酶 DNA 结合蛋白 6 (CHD6) 是 IFN-κ 抗病毒活性的主要效应物，但不是 IFN-α 或 IFN 的抗病毒活性的主要效应物-β。CHD6 的诱导需要 I 型 IFN 受体亚基 IFNAR1 和 IFNAR2、丝裂原活化蛋白激酶 (MAPK) p38、和转录因子 c-Fos 但独立于信号转导和转录激活因子 1 (STAT1) 活性。此外，我们表明用 IFN-κ 预处理可以保护小鼠免受致命的流感病毒攻击。总之，我们的研究结果确定了抑制 A 型流感病毒的 IFN-κ 特异性途径，并提供证据表明 IFN-κ 可能具有作为针对 A 型流感病毒的预防和治疗剂的潜力。