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IFI16 directly senses viral RNA and enhances RIG-I transcription and activation to restrict influenza virus infection
Nature Microbiology ( IF 20.5 ) Pub Date : 2021-05-13 , DOI: 10.1038/s41564-021-00907-x
Zhimin Jiang 1 , Fanhua Wei 2 , Yuying Zhang 3 , Tong Wang 1 , Weihua Gao 1 , Shufang Yu 2 , Honglei Sun 1 , Juan Pu 1 , Yipeng Sun 1 , Mingyang Wang 1 , Qi Tong 1 , Chengjiang Gao 4 , Kin-Chow Chang 5 , Jinhua Liu 1
Affiliation  

The retinoic acid-inducible gene I (RIG-I) receptor senses cytoplasmic viral RNA and activates type I interferons (IFN-I) and downstream antiviral immune responses. How RIG-I binds to viral RNA and how its activation is regulated remains unclear. Here, using IFI16 knockout cells and p204-deficient mice, we demonstrate that the DNA sensor IFI16 enhances IFN-I production to inhibit influenza A virus (IAV) replication. IFI16 positively upregulates RIG-I transcription through direct binding to and recruitment of RNA polymerase II to the RIG-I promoter. IFI16 also binds to influenza viral RNA via its HINa domain and to RIG-I protein with its PYRIN domain, thus promoting IAV-induced K63-linked polyubiquitination and RIG-I activation. Our work demonstrates that IFI16 is a positive regulator of RIG-I signalling during influenza virus infection, highlighting its role in the RIG-I-like-receptor-mediated innate immune response to IAV and other RNA viruses, and suggesting its possible exploitation to modulate the antiviral response.



中文翻译:


IFI16直接感知病毒RNA并增强RIG-I转录和激活以限制流感病毒感染



视黄酸诱导基因 I (RIG-I) 受体感知细胞质病毒 RNA,并激活 I 型干扰素 (IFN-I) 和下游抗病毒免疫反应。 RIG-I 如何与病毒 RNA 结合以及如何调节其激活仍不清楚。在这里,使用 IFI16 敲除细胞和 p204 缺陷小鼠,我们证明 DNA 传感器 IFI16 增强 IFN-I 的产生,从而抑制甲型流感病毒 (IAV) 复制。 IFI16 通过直接结合 RNA 聚合酶 II 并将其募集至RIG-I启动子,正向上调RIG-I转录。 IFI16 还通过其 HINa 结构域与流感病毒 RNA 结合,并通过其 PYRIN 结构域与 RIG-I 蛋白结合,从而促进 IAV 诱导的 K63 连接的多聚泛素化和 RIG-I 激活。我们的工作表明,IFI16 是流感病毒感染期间 RIG-I 信号传导的正调节因子,强调了其在 RIG-I 样受体介导的针对 IAV 和其他 RNA 病毒的先天免疫反应中的作用,并表明其可能用于调节抗病毒反应。

更新日期:2021-05-13
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