DDX19 Inhibits Type I Interferon Production by Disrupting TBK1-IKK epsilon-IRF3 Interactions and Promoting TBK1 and IKK epsilon Degradation

文献类型： 外文期刊

第一作者： Zhang, Kunli

作者： Zhang, Kunli;Zhang, Yuanfeng;Xue, Juan;Meng, Qingwen;Liu, Hongyang;Bi, Caihong;Li, Changyao;Hu, Liang;Yu, Huibin;Bu, Zhigao;He, Xijun;Li, Jiangnan;Huang, Li;Weng, Changjiang;Xiong, Tao;Yang, Yuying;Cui, Shangjin

作者机构：

期刊名称：CELL REPORTS （ 影响因子：9.423； 五年影响因子：10.394 ）

ISSN： 2211-1247

年卷期： 2019 年 26 卷 5 期

页码：

收录情况： SCI

摘要： DExD/H-box helicase members are key receptors for recognizing viral nucleic acids, and they regulate retinoic acid-inducible gene I (RIG-I)-like receptor (RLR)-mediated type I interferon (IFN) production. Here, we report that the DExD/H-box helicase family member DExD/H-box RNA helicase 19 (DDX19) is a negative regulator of type I IFN production. Ectopic expression of DDX19 suppressed poly(I: C) (polyinosinic-polycytidylic acid)-and Sendai-virus-induced type I IFN production, whereas knockdown of DDX19 expression enhanced type I IFN production. Mechanistically, DDX19 inhibited TANK-binds kinase 1 (TBK1)-and inhibitor-kappa b kinase epsilon (IKK epsilon)-mediated phosphorylation of interferon regulatory factor 3 (IRF3) by disrupting the interaction between TBK1 or IKK and IRF3. Additionally, DDX19 recruited Lamtor2 and then formed the TBK1-IKK epsilon-Lamtor2-DDX19-IRF3 complex to suppress IFN production by promoting TBK1 and IKK epsilon degradation. We generated Ddx19 knockout mice using transcription activator-like effector nucleases (TALENs) and found that Ddx19 deficiency in vivo augmented type I IFN production, resulting in suppression of encephalomyocarditis virus replication. These data show that DDX19 is an important negative regulator of RLR-mediated type I IFN production.

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