Helicase protein DDX11 as a novel antiviral factor promoting RIG-I-MAVS-mediated signaling pathway

文献类型： 外文期刊

第一作者： Zhang, Jiyu

作者： Zhang, Jiyu;Zhang, Liaoyuan;Liu, Dakai;Shi, Hongyan;Zhang, Xin;Chen, Jianfei;Yang, Xiaoman;Zeng, Miaomiao;Zhang, Jialin;Feng, Tingshuai;Zhu, Xiaoyuan;Jing, Zhaoyang;Ji, Zhaoyang;Shi, Da;Feng, Li

作者机构：

关键词： DDX11; RIG-I; MAVS; IFN

期刊名称：MBIO （ 影响因子：4.7； 五年影响因子：5.5 ）

ISSN：

年卷期： 2024 年 15 卷 12 期

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收录情况： SCI

摘要： Type Iota interferon (IFN) production mediated by retinoic acid-inducible gene 1 (RIG-I) and mitochondrial antiviral signaling protein (MAVS) is essential for antiviral innate immune responses. Here, we report the identification of a novel co-sensor for cytosolic nucleic acids: DEAD/H-box helicase 11 (DDX11), a member of the DExD/H (Asp-Glu-x-Asp/His)-box helicase family. Knockdown or knockout of DDX11 attenuated the ability of cells to increase IFN-beta, IFN-stimulated gene 56, and C-X-C motif chemokine ligand 10 in response to SeV and poly (I:C) by blocking the activation of TANK-binding kinase 1 and IFN regulatory factor 3. Nucleic acid sensing by DDX11 was independent of the stimulator of IFN genes but was dependent on RIG-I and MAVS. DDX11 regulated RIG-I-MAVS-mediated IFN signaling by specifically interacting with nucleic acid, RIG-I, and MAVS to enhance RIG-I-double-strand RNA and RIG-I-MAVS binding affinity. Overall, our results identified a critical role for DDX11 in the innate immune response and provided molecular insights into the mechanisms by which DDX11 recognized cytosolic nucleic acid and interacted with RIG-Iota and MAVS for potent IFN signaling and antiviral immunity.

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