Nucleophosmin 1 inhibits the replication of influenza A virus by competitively binding viral RNA with viral proteins

Yingying Yu; Qian Wang; Yanli Wei; Junwen Liu; Guangwen Wang; Zhengxiang Wang; Wentao Shen; Lu Han; Chengjun Li; Cao-Qi Lei; Shuai Xu; Qiyun Zhu

doi:10.1016/j.virs.2025.04.007

June 2025

. doi: 10.1016/j.virs.2025.04.007

Citation: Yingying Yu, Qian Wang, Yanli Wei, Junwen Liu, Guangwen Wang, Zhengxiang Wang, Wentao Shen, Lu Han, Chengjun Li, Cao-Qi Lei, Shuai Xu, Qiyun Zhu. Nucleophosmin 1 inhibits the replication of influenza A virus by competitively binding viral RNA with viral proteins .VIROLOGICA SINICA, 2025, 40(3) : 388-400. http://dx.doi.org/10.1016/j.virs.2025.04.007

核磷蛋白NPM1通过与病毒蛋白竞争结合病毒RNA抑制A型流感病毒的复制

余影影 ^a ,
王倩 ^a ,
韦严丽 ^a ,
刘君雯 ^a ,
王广文 ^b ,
王正祥 ^a ,
申汶涛 ^a ,
韩璐 ^a ,
李呈军 ^b ,
雷曹琦 ^c ,
徐帅 ^a,d,, ,
朱启运 ^a,,

a 动物疫病防控全国重点实验室, 兰州大学动物医学与生物安全学院;
b 动物疫病防控全国重点实验室, 中国农业科学院哈尔滨兽医研究所;
c 病毒学国家重点实验室, 武汉大学;
d 甘肃省病原生物学基础学科研究中心

通讯作者： 徐帅, xushuai@caas.cn; 朱启运, zhuqiyun@caas.cn
收稿日期： 2024-12-16
录用日期： 2025-04-27

摘要

A型流感病毒（IAV）是一种单股负链RNA病毒，对动物和人类健康构成持续威胁。在IAV感染的细胞中，宿主RNA结合蛋白通过直接与病毒RNA结合，在IAV的生命周期中发挥着关键作用。本研究中，我们揭示了宿主核磷蛋白NPM1在IAV复制中的作用。我们发现，NPM1可直接与病毒RNA（vRNA）结合，并抑制多种亚型IAV的复制。NPM1与vRNA的结合可竞争性地降低病毒核糖核蛋白复合物的组装和病毒聚合酶的活性，从而减少子代病毒RNA和病毒的生成。NPM1的RNA结合活性对其抗流感功能起着关键作用，而T199/T219/T234/T237是NPM1蛋白结合病毒RNA的关键位点。综上所述，本研究结果表明，NPM1作为一种RNA结合蛋白，可以通过与流感病毒vRNA相互作用抑制病毒复制。
- 核磷蛋白NPM1
- , A型流感病毒
- , RNA结合
- , 病毒RNA
- , 病毒聚合酶

Nucleophosmin 1 inhibits the replication of influenza A virus by competitively binding viral RNA with viral proteins

Yingying Yu ^a ,
Qian Wang ^a ,
Yanli Wei ^a ,
Junwen Liu ^a ,
Guangwen Wang ^b ,
Zhengxiang Wang ^a ,
Wentao Shen ^a ,
Lu Han ^a ,
Chengjun Li ^b ,
Cao-Qi Lei ^c ,
Shuai Xu ^a,d,, ,
Qiyun Zhu ^a,,

a. State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730000, China;
b. State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150069, China;
c. State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, 430072, China;
d. Gansu Province Research Center for Basic Disciplines of Pathogen Biology, Lanzhou, 730046, China

Corresponding author: Shuai Xu, xushuai@caas.cn Qiyun Zhu, zhuqiyun@caas.cn
Received Date: 16 December 2024
Accepted Date: 27 April 2025

Abstract

Influenza A viruses (IAVs) are single-stranded negative-sense RNA viruses that continually challenge animal and human health. In IAV-infected cells, host RNA-binding proteins play key roles in the life cycle of IAV by directly binding to viral RNA. Here, we examined the role of the host RNA-binding protein nucleophosmin-1 (NPM1) in IAV replication. We found that, as a nucleolar phosphoprotein, NPM1 directly binds to viral RNA (vRNA) and inhibits the replication of various subtypes of IAV. NPM1 binding to vRNA competitively reduces the assembly of the viral ribonucleoprotein complex and the viral polymerase activity, thereby reducing the generation of progeny viral RNA and virions. The RNA-binding activity of NPM1, with the key residues T199, T219, T234, and T237, is essential for its anti-influenza function. Taken together, our findings demonstrate that NPM1 acts as an RNA-binding protein and interacts with IAV vRNA to suppress viral replication.
- Nucleophosmin-1 (NPM1)
- , Influenza A virus (IAV)
- , RNA binding
- , Viral RNA
- , Viral polymerase

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10.1016j.virs.2025.04.007-ESM.docx