Influenza A Virus Polymerase Recruits the RNA Helicase DDX19 to Promote the Nuclear Export of Viral mRNAs.
Influenza A Virus Polymerase Recruits the RNA Helicase DDX19 to Promote the Nuclear Export of Viral mRNAs.
复制标题
流感病毒聚合酶募集RNA解旋酶DDX19以促进病毒mRNA的核输出。
DOI：
10.1038/srep33763
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发表时间：
2016-09-22
影响因子：
4.6
通讯作者：
Naffakh N
中科院分区：
文献类型：
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作者：
Diot C;Fournier G;Dos Santos M;Magnus J;Komarova A;van der Werf S;Munier S;Naffakh N
加强对甲型流感病毒（IAV）有效复制所需的宿主因素的了解对于解决与致病性相关的问题和确定抗病毒药物开发的靶点至关重要。在这里，我们专注于IAV和DExD-box RNA解旋酶（DDX）之间的相互作用，它通过重塑RNA-RNA或RNA-蛋白质复合物在细胞RNA代谢中发挥关键作用。我们对35种人类DDX蛋白进行了靶向RNAi筛选，以鉴定参与IAV生命周期的蛋白。DDX 19是一个很大的打击。在DDX 19耗尽的细胞中，病毒RNA和蛋白质的积累被延迟，并且感染性IAV颗粒的产生强烈减少。我们发现DDX 19与无内含子、未剪接和剪接的IAV mRNA相关，并促进其核输出。此外，我们证明了DDX 19和病毒聚合酶之间的RNA非依赖性关联，该关联由DDX 19的ATP酶活性调节。我们的研究结果提供了一个模型，其中DDX 19被招募到受感染细胞核中的病毒mRNA中，以增强其核输出。从这种病毒-宿主相互作用中获得的信息提高了对IAV复制周期和DDX 19细胞功能的理解。
Enhancing the knowledge of host factors that are required for efficient influenza A virus (IAV) replication is essential to address questions related to pathogenicity and to identify targets for antiviral drug development. Here we focused on the interplay between IAV and DExD-box RNA helicases (DDX), which play a key role in cellular RNA metabolism by remodeling RNA-RNA or RNA-protein complexes. We performed a targeted RNAi screen on 35 human DDX proteins to identify those involved in IAV life cycle. DDX19 was a major hit. In DDX19-depleted cells the accumulation of viral RNAs and proteins was delayed, and the production of infectious IAV particles was strongly reduced. We show that DDX19 associates with intronless, unspliced and spliced IAV mRNAs and promotes their nuclear export. In addition, we demonstrate an RNA-independent association between DDX19 and the viral polymerase, that is modulated by the ATPase activity of DDX19. Our results provide a model in which DDX19 is recruited to viral mRNAs in the nucleus of infected cells to enhance their nuclear export. Information gained from this virus-host interaction improves the understanding of both the IAV replication cycle and the cellular function of DDX19.
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影响因子：
3.7
作者：
Ge X;Rameix-Welti MA;Gault E;Chase G;dos Santos Afonso E;Picard D;Schwemmle M;Naffakh N
通讯作者：
Naffakh N
影响因子：
5.4
作者：
Martínez-Alonso M;Hengrung N;Fodor E
通讯作者：
Fodor E
影响因子：
3.7
作者：
Folkmann, Andrew W.;Noble, Kristen N.;Wente, Susan R.
通讯作者：
Wente, Susan R.
影响因子：
3.1
作者：
Kawakami, Eiryo;Watanabe, Tokiko;Fujii, Ken;Goto, Hideo;Watanabe, Shinji;Noda, Takeshi;Kawaoka, Yoshihiro
通讯作者：
Kawaoka, Yoshihiro
影响因子：
30.5
作者：
通讯作者：
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