生物
α病毒
核糖核酸
病毒学
病毒复制
甲病毒感染
基孔肯雅
RNA解旋酶A
RNA依赖性RNA聚合酶
RNA结合蛋白
蟾蜍科
解旋酶
遗传学
病毒
基因
作者
Iulia Tapescu,Frances Taschuk,Swechha M. Pokharel,Oleksandr Zginnyk,Max B Ferretti,P Bailer,Kanupryia Whig,Emily A. Madden,Mark T. Heise,D. Schultz,Sara Cherry
出处
期刊:Molecular Cell
[Elsevier]
日期:2023-11-01
卷期号:83 (22): 4174-4189.e7
被引量:1
标识
DOI:10.1016/j.molcel.2023.10.008
摘要
Alphaviruses are a large group of re-emerging arthropod-borne RNA viruses. The compact viral RNA genomes harbor diverse structures that facilitate replication. These structures can be recognized by antiviral cellular RNA-binding proteins, including DExD-box (DDX) helicases, that bind viral RNAs to control infection. The full spectrum of antiviral DDXs and the structures that are recognized remain unclear. Genetic screening identified DDX39A as antiviral against the alphavirus chikungunya virus (CHIKV) and other medically relevant alphaviruses. Upon infection, the predominantly nuclear DDX39A accumulates in the cytoplasm inhibiting alphavirus replication, independent of the canonical interferon pathway. Biochemically, DDX39A binds to CHIKV genomic RNA, interacting with the 5′ conserved sequence element (5′CSE), which is essential for the antiviral activity of DDX39A. Altogether, DDX39A relocalization and binding to a conserved structural element in the alphavirus genomic RNA attenuates infection, revealing a previously unknown layer to the cellular control of infection.
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