Ling Yue-Huan, Wang Hao, Han Mei-Qing, Wang Di, Hu Yi-Xiang, Zhou Kun, Li Yan
Department of Veterinary Medicine and Institute of Preventive Veterinary Sciences, Zhejiang University College of Animal Sciences, Hangzhou, Zhejiang, China.
Hainan Institute, Zhejiang University, Sanya, Hainan, China.
Front Microbiol. 2022 Aug 16;13:895779. doi: 10.3389/fmicb.2022.895779. eCollection 2022.
Transcription and replication of the influenza A virus (IAV) genome take place in the nucleus of infected cells, which rely on host factors to aid viral ribonucleoprotein (vRNP) to cross the nuclear pore complex (NPC) and complete the bidirectional nucleocytoplasmic trafficking. Here, we showed that nucleoporin 85 (NUP85), a component of NPC, interacted with RNP subunits polymerase basic 1 (PB1) and polymerase basic 2 (PB2) in an RNA-dependent manner during IAV infection. Knockdown of NUP85 delayed the nuclear import of vRNP, PB1 and PB2, inhibiting polymerase activity and ultimately suppressing viral replication. Further analysis revealed that NUP85 assisted the binding of PB1 to nuclear transport factor Ran-binding protein 5 (RanBP5) and the binding of PB2 to nuclear transport factor importin α1 and importin α7. We also found that NUP85 expression was downregulated upon IAV infection. Together, our study demonstrated that NUP85 positively regulated IAV infection by interacting with viral PB1 and PB2, which may provide new insight into the process of vRNP nuclear import and a novel target for effective antivirals.
甲型流感病毒（IAV）基因组的转录和复制在受感染细胞的细胞核中进行，这依赖于宿主因子来帮助病毒核糖核蛋白（vRNP）穿过核孔复合体（NPC）并完成双向核质运输。在此，我们表明核孔蛋白85（NUP85）是NPC的一个组成部分，在IAV感染期间以RNA依赖的方式与RNP亚基聚合酶基本蛋白1（PB1）和聚合酶基本蛋白2（PB2）相互作用。敲低NUP85会延迟vRNP、PB1和PB2的核输入，抑制聚合酶活性并最终抑制病毒复制。进一步分析表明，NUP85有助于PB1与核转运因子Ran结合蛋白5（RanBP5）的结合以及PB2与核转运因子输入蛋白α1和输入蛋白α7的结合。我们还发现，IAV感染后NUP85的表达下调。总之，我们的研究表明，NUP85通过与病毒PB1和PB2相互作用对IAV感染起正向调节作用，这可能为vRNP核输入过程提供新的见解，并为有效的抗病毒药物提供新的靶点。
