Heterogeneous Ribonucleoprotein A1 (hnRNPA1) Interacts with the Nucleoprotein of the Influenza a Virus and Impedes Virus Replication.
Heterogeneous Ribonucleoprotein A1 (hnRNPA1) Interacts with the Nucleoprotein of the Influenza a Virus and Impedes Virus Replication.
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异质核糖核蛋白A1（hnRNPA1）与甲型流感病毒的核蛋白相互作用并阻碍病毒复制。
DOI：
10.3390/v14020199
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发表时间：
2022-01-20
期刊：
影响因子：
--
通讯作者：
Lal SK
中科院分区：
文献类型：
--
作者：
Kaur R;Batra J;Stuchlik O;Reed MS;Pohl J;Sambhara S;Lal SK
甲型流感病毒（IAV）与其他病毒一样，依赖于宿主细胞机制进行复制和产生后代。病毒和宿主之间的关系是复杂的，由病毒和宿主蛋白质组之间的许多空间和时间相互作用形成，最终决定疾病的结果。因此，必须确定宿主-病毒相互作用作为疾病病因的关键决定因素。异质性核糖核蛋白A1（hnRNPA 1）是一种RNA结合蛋白，参与许多DNA和RNA病毒的生命周期;然而，它在IAV中的作用尚未被发现。在这里，我们报告了人hnRNPA 1在病毒复制周期的不同时间点与哺乳动物细胞中IAV的核蛋白（NP）发生物理相互作用。时间分布的研究表明，在NP转染和IAV感染的哺乳动物细胞中，hnRNPA 1和NP共定位于细胞核和线粒体的相同细胞环境中。有趣的是，hnRNPA 1影响NP基因表达和影响病毒复制。最重要的是，hnRNPA 1敲低导致NP表达显著增加，并在IAV感染的A549细胞中增强病毒复制（93.82%）。相反，hnRNPA 1过表达在mRNA和蛋白水平上降低NP表达，并阻碍病毒复制（60.70%），表明拮抗功能。总之，这项研究的结果表明，细胞hnRNPA 1在宿主中起着迄今为止未知的保护作用，并可能作为抗病毒靶点开发基于宿主的抗IAV治疗药物。
Influenza A virus (IAV), like other viruses, depends on the host cellular machinery for replication and production of progeny. The relationship between a virus and a host is complex, shaped by many spatial and temporal interactions between viral and host proteome, ultimately dictating disease outcome. Therefore, it is imperative to identify host-virus interactions as crucial determinants of disease pathogenies. Heterogeneous ribonucleoprotein A1 (hnRNPA1) is an RNA binding protein involved in the life cycle of many DNA and RNA viruses; however, its role in IAV remains undiscovered. Here we report that human hnRNPA1 physically interacts with the nucleoprotein (NP) of IAV in mammalian cells at different time points of the viral replication cycle. Temporal distribution studies identify hnRNPA1 and NP co-localize in the same cellular milieu in both nucleus and mitochondria in NP-transfected and IAV-infected mammalian cells. Interestingly, hnRNPA1 influenced NP gene expression and affected viral replication. Most importantly, hnRNPA1 knockdown caused a significant increase in NP expression and enhanced viral replication (93.82%) in IAV infected A549 cells. Conversely, hnRNPA1 overexpression reduced NP expression at the mRNA and protein levels and impeded virus replication by (60.70%), suggesting antagonistic function. Taken together, results from this study demonstrate that cellular hnRNPA1 plays a protective role in the host hitherto unknown and may hold potential as an antiviral target to develop host-based therapeutics against IAV.
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影响因子：
5.4
作者：
Kneller, Elizabeth L. Pettit;Connor, John H.;Lyles, Douglas S.
通讯作者：
Lyles, Douglas S.
DOI：
10.1042/bcj20160499
发表时间：
2017-04-07
期刊：
The Biochemical journal
影响因子：
--
作者：
Harrison AF;Shorter J
通讯作者：
Shorter J
影响因子：
3.3
作者：
Kress E;Baydoun HH;Bex F;Gazzolo L;Duc Dodon M
通讯作者：
Duc Dodon M
影响因子：
5.6
作者：
Jean-Philippe J;Paz S;Caputi M
通讯作者：
Caputi M
影响因子：
7.6
作者：
Lee SM;Yen HL
通讯作者：
Yen HL