The Host Factor ANP32A Is Required for Influenza A Virus vRNA and cRNA Synthesis.
The Host Factor ANP32A Is Required for Influenza A Virus vRNA and cRNA Synthesis.
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DOI：
10.1128/jvi.02092-21
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发表时间：
2022-02-23
影响因子：
5.4
通讯作者：
Te Velthuis AJW
中科院分区：
文献类型：
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作者：
Nilsson-Payant BE;tenOever BR;Te Velthuis AJW
甲型流感病毒是负义 RNA 病毒，依靠自身的病毒复制机制来复制和转录其分段的单链 RNA 基因组。病毒RNA在其中复制的病毒核糖核蛋白复合物由RNA基因组缠绕的核蛋白支架和催化病毒复制的异三聚体RNA依赖性RNA聚合酶组成。 RNA 聚合酶通过称为 cRNA 的复制中间体复制病毒 RNA (vRNA)，然后使用该 cRNA 生成更多 vRNA 副本。为了确保新的 cRNA 和 vRNA 分子与核糖核蛋白相关并可以在其中进行扩增，活性 RNA 聚合酶会招募第二个聚合酶来封装 cRNA 或 vRNA。宿主因子 ANP32A 已被证明对于病毒复制和促进病毒 RNA 聚合酶之间二聚体的形成至关重要。哺乳动物和鸟类 ANP32A 蛋白之间的差异足以限制病毒复制。有人提出，ANP32A 仅是从 cRNA 合成 vRNA 分子所必需的，反之则不然。然而，这种观点与最近的分子证据并不相符。在这里，我们使用小基因组测定、病毒感染和病毒启动子突变来证明 ANP32A 对于 vRNA 和 cRNA 合成至关重要。此外，我们表明，ANP32A 不仅是活跃复制聚合酶所需要的，而且也是包裹新生病毒 RNA 产物的聚合酶所不需要的。总的来说，这些结果为甲型流感病毒复制和宿主适应提供了新的见解。重要性 人畜共患甲型禽流感病毒对全球健康构成持续威胁，并有可能引起大流行。宿主因子 ANP32A 的物种变异在支持哺乳动物宿主中甲型禽流感病毒 RNA 聚合酶的活性方面发挥着关键作用。在这里，我们证明 ANP32A 在甲型流感病毒复制周期的两个阶段发挥作用，支持最近的结构实验，与其基本作用相符。了解 ANP32A 如何支持病毒 RNA 聚合酶活性以及它如何支持哺乳动物宿主中的禽类聚合酶功能对于了解甲型流感病毒复制和开发针对甲型流感病毒的抗病毒策略非常重要。
Influenza A viruses are negative-sense RNA viruses that rely on their own viral replication machinery to replicate and transcribe their segmented single-stranded RNA genome. The viral ribonucleoprotein complexes in which viral RNA is replicated consist of a nucleoprotein scaffold around which the RNA genome is wound, and a heterotrimeric RNA-dependent RNA polymerase that catalyzes viral replication. The RNA polymerase copies the viral RNA (vRNA) via a replicative intermediate, called the cRNA, and subsequently uses this cRNA to make more vRNA copies. To ensure that new cRNA and vRNA molecules are associated with ribonucleoproteins in which they can be amplified, the active RNA polymerase recruits a second polymerase to encapsidate the cRNA or vRNA. Host factor ANP32A has been shown to be essential for viral replication and to facilitate the formation of a dimer between viral RNA polymerases. Differences between mammalian and avian ANP32A proteins are sufficient to restrict viral replication. It has been proposed that ANP32A is only required for the synthesis of vRNA molecules from cRNA but not vice versa. However, this view does not match recent molecular evidence. Here we use minigenome assays, virus infections, and viral promoter mutations to demonstrate that ANP32A is essential for both vRNA and cRNA synthesis. Moreover, we show that ANP32A is not only needed for the actively replicating polymerase, but not for the polymerase that is encapsidating nascent viral RNA products. Overall, these results provide new insights into influenza A virus replication and host adaptation. IMPORTANCE Zoonotic avian influenza A viruses pose a constant threat to global health, and they have the potential to cause pandemics. Species variations in host factor ANP32A play a key role in supporting the activity of avian influenza A virus RNA polymerases in mammalian hosts. Here we show that ANP32A acts at two stages in the influenza A virus replication cycle, supporting recent structural experiments, in line with its essential role. Understanding how ANP32A supports viral RNA polymerase activity and how it supports avian polymerase function in mammalian hosts is important for understanding influenza A virus replication and the development of antiviral strategies against influenza A viruses.
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影响因子：
16.6
作者：
Domingues, Patricia;Eletto, Davide;Hale, Benjamin G.
通讯作者：
Hale, Benjamin G.
影响因子：
64.8
作者：
ALMOND, JW
通讯作者：
ALMOND, JW
影响因子：
3.5
作者：
Matilla, A;Radrizzani, M
通讯作者：
Radrizzani, M
影响因子：
5.4
作者：
Nilsson BE;Te Velthuis AJW;Fodor E
通讯作者：
Fodor E
DOI：
10.1038/s41572-018-0002-y
发表时间：
2018-06-28
期刊：
Nature reviews. Disease primers
影响因子：
--
作者：
Krammer F;Smith GJD;Fouchier RAM;Peiris M;Kedzierska K;Doherty PC;Palese P;Shaw ML;Treanor J;Webster RG;García-Sastre A
通讯作者：
García-Sastre A