P200 family protein IFI204 negatively regulates type I interferon responses by targeting IRF7 in nucleus

Autoři: Liu Cao aff001;  Yanxi Ji aff001;  Lanyi Zeng aff001;  Qianyun Liu aff001;  Zhen Zhang aff001;  Shuting Guo aff003;  Xiaolong Guo aff004;  Yongjia Tong aff004;  Xiaolu Zhao aff004;  Chun-Mei Li aff002;  Yu Chen aff001;  Deyin Guo aff002
Působiště autorů: State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China aff001;  School of Medicine, Sun Yat-sen University, Guangzhou, China aff002;  School of Basic Medical Sciences, Wuhan University, Wuhan, China aff003;  College of Life Sciences, Wuhan University, Wuhan, China aff004
Vyšlo v časopise: P200 family protein IFI204 negatively regulates type I interferon responses by targeting IRF7 in nucleus. PLoS Pathog 15(10): e32767. doi:10.1371/journal.ppat.1008079
Kategorie: Research Article
doi: 10.1371/journal.ppat.1008079


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.

Klíčová slova:

Co-immunoprecipitation – DNA-binding proteins – Enzyme-linked immunoassays – Interferons – Plasmid construction – RNA viruses – Small interfering RNAs – ssRNA viruses


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