P200 family protein IFI204 negatively regulates type I interferon responses by targeting IRF7 in nucleus
P200 family protein IFI204 negatively regulates type I interferon responses by targeting IRF7 in nucleus
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P200家族蛋白IFI204通过靶向细胞核中的IRF7负向调节I型干扰素反应
DOI：
10.1371/journal.ppat.1008079
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发表时间：
2019-10-01
期刊：
影响因子：
6.7
通讯作者：
Guo, Deyin
中科院分区：
文献类型：
--
作者：
Cao, Liu;Ji, Yanxi;Guo, Deyin
据报道，干扰素诱导的p200家族蛋白IFI204参与DNA传感，并随后诱导I型干扰素和促炎介质的产生。然而，其在抗病毒天然免疫信号通路中的调节功能尚不清楚。在这里，我们报告了一种新的作用，IFI204，特异性抑制IRF7介导的I型干扰素反应在病毒感染。IFI204和其他p200家族蛋白在小鼠肝炎冠状病毒感染的骨髓来源的树突状细胞中高度表达IFI204在细胞核内通过其HIN结构域与IRF7相互作用，阻止IRF7与其相应启动子的结合。此外，具有HIN结构域的其他p200家族蛋白也可以抑制IRF7介导的I型干扰素。这些结果表明，干扰素诱导的p200家族蛋白（例如IFI204）除了在DNA病毒感染早期对I型干扰素反应具有正调节作用外，还可以在RNA病毒感染后负调节IRF7介导的I型干扰素反应，以避免过度炎症反应对宿主造成不必要的损害。
Interferon-inducible p200 family protein IFI204 was reported to be involved in DNA sensing, and subsequently induces the production of type I interferons and proinflammatory mediators. However, its function in the regulation of antiviral innate immune signaling pathway remains unclear. Here we reported a novel role of IFI204 that specifically inhibits the IRF7-mediated type I interferons response during viral infection. IFI204 and other p200 family proteins are highly expressed in mouse hepatitis coronavirus-infected bone marrow-derived dendritic cells. The abundant IFI204 could significantly interact with IRF7 in nucleus by its HIN domain and prevent the binding of IRF7 with its corresponding promoter. Moreover, other p200 family proteins that possess HIN domain could also inhibit the IRF7-mediated type I interferons. These results reveal that, besides the positive regulation function in type I interferon response at the early stage of DNA virus infection, the interferon-inducible p200 family proteins such as IFI204 could also negatively regulate the IRF7-mediated type I interferon response after RNA virus infection to avoid unnecessary host damage from hyper-inflammatory responses.