Altering Intracellular Localization of the RNA Interference Factors by Influenza A Virus Non-structural Protein 1.
Altering Intracellular Localization of the RNA Interference Factors by Influenza A Virus Non-structural Protein 1.
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通过甲型流感病毒非结构蛋白 1 改变 RNA 干扰因子的细胞内定位。
DOI：
10.3389/fmicb.2020.590904
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发表时间：
2020
影响因子：
5.2
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Wang H;Tian Z;Xu Y;Wang Q;Ding SW;Li Y
甲型流感病毒（IAV）在人类中引起季节性感染和周期性大流行。IAV的非结构蛋白1（NS 1）是天然免疫应答的主要拮抗剂，在流感发病机制中起关键作用。然而，IAV NS 1破坏宿主细胞稳态的机制仍然知之甚少。在这里，我们表明，NS 1从WSN株，但不是PR 8株，IAV的表达，显着诱导宿主RNA干扰（RNAi）因子，如Argonaute-2和microRNA 16的核进口。我们发现，IAV-PR 8 NS 1的第101位（D101 H）的天冬氨酸被组氨酸取代的单个残基足以诱导核输入过程，并增强IAV-PR 8在小鼠中的毒力。然而，我们没有观察到野生型和突变体IAV-PR 8之间的病毒滴度或肺组织中的干扰素反应的诱导的显着差异，表明在哺乳动物宿主中的IAV的毒力测定的新的作用NS 1。此外，我们对NCBI数据库中所有IAV亚型的69，057个NS 1序列进行了生物信息学分析，结果显示IAV-WSN的NS 1-H101基因在1933年分离的H1N1病毒中广泛存在，但在1940年后完全消失。因此，IAV NS 1（H101）是IAV进化过程中选择的突变，表明突变H101赋予重要的生物学表型。
Influenza A virus (IAV) causes seasonal infections and periodic pandemics in humans. The non-structural protein 1 (NS1) of IAV is the main viral antagonist of the innate immune responses that play a key role in influenza pathogenesis. However, the mechanism to disrupt the host cell homeostasis by IAV NS1 remains poorly understood. Here, we show that expression of NS1 from the WSN strain, but not PR8 strain, of IAV, markedly induced nuclear import of the host RNA interference (RNAi) factors such as Argonaute-2 and microRNA 16. We found that the single residue substitution of aspartic acid with histidine at position 101 (D101H) of IAV-PR8 NS1 was sufficient to induce the nuclear import process and to enhance the virulence of IAV-PR8 in mice. However, we observed no significant differences between the wild-type and mutant IAV-PR8 in virus titers or induction of the interferon response in lung tissues, indicating a novel role of NS1 in the virulence determination of IAV in a mammalian host. Moreover, our bioinformatic analysis of 69,057 NS1 sequences from all IAV subtypes deposited in the NCBI database revealed that the NS1-H101 gene of IAV-WSN was widespread among H1N1 viruses isolated in 1933 but disappeared completely after 1940. Thus, IAV NS1 (H101) is a mutation selected against during evolution of IAV, suggesting that mutation H101 confers an important biological phenotype.
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DOI：
10.1073/pnas.031575198
发表时间：
2001-02-27
影响因子：
11.1
作者：
Basler, CF;Reid, AH;Taubenberger, JK
通讯作者：
Taubenberger, JK
影响因子：
7
作者：
Fukuyama S;Kawaoka Y
通讯作者：
Kawaoka Y
影响因子：
64.8
作者：
Denli, AM;Tops, BBJ;Hannon, GJ
通讯作者：
Hannon, GJ
不同宿主物种甲型流感病毒（IAV）感染的 A549 细胞中 microRNA-mRNA 表达的综合分析
影响因子：
5
作者：
Gao, Jie;Gao, Lingxi;Fan, Xiaohui
通讯作者：
Fan, Xiaohui
影响因子：
64.8
作者：
Bernstein, E;Caudy, AA;Hannon, GJ
通讯作者：
Hannon, GJ