生物
翻译(生物学)
细胞生物学
先天免疫系统
核糖体
病毒复制
干扰素
抗病毒蛋白
心理压抑
干扰素刺激基因
病毒学
作者
Jack Chun-Chieh Hsu,Maudry Laurent-Rolle,Joanna B Pawlak,Hongjie Xia,Amit Kunte,Jia Shee Hee,Jaechul Lim,Lawrence D Harris,James M Wood,Gary B Evans,Pei-Yong Shi,Tyler L Grove,Steven C Almo,Peter Cresswell
出处
期刊:Molecular Cell
[Elsevier]
日期:2022-05-05
卷期号:82 (9): 1631-1642.e6
标识
DOI:10.1016/j.molcel.2022.02.031
摘要
Innate immune responses induce hundreds of interferon-stimulated genes (ISGs). Viperin, a member of the radical S-adenosyl methionine (SAM) superfamily of enzymes, is the product of one such ISG that restricts the replication of a broad spectrum of viruses. Here, we report a previously unknown antiviral mechanism in which viperin activates a ribosome collision-dependent pathway that inhibits both cellular and viral RNA translation. We found that the radical SAM activity of viperin is required for translation inhibition and that this is mediated by viperin's enzymatic product, 3'-deoxy-3',4'-didehydro-CTP (ddhCTP). Viperin triggers ribosome collisions and activates the MAPKKK ZAK pathway that in turn activates the GCN2 arm of the integrated stress response pathway to inhibit translation. The study illustrates the importance of translational repression in the antiviral response and identifies viperin as a translation regulator in innate immunity.
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