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甲型 H1N1 流感病毒蛋白 NS2 通过靶向 IRF7 抑制先天免疫反应。

H1N1 Influenza A Virus Protein NS2 Inhibits Innate Immune Response by Targeting IRF7.

机构信息

College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China.

State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China.

出版信息

Viruses. 2022 Oct 31;14(11):2411. doi: 10.3390/v14112411.

DOI:10.3390/v14112411
PMID:36366509
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9694023/
Abstract

Influenza A virus (IAV) is a globally distributed zoonotic pathogen and causes a highly infectious respiratory disease with high morbidity and mortality in humans and animals. IAV has evolved various strategies to counteract the innate immune response, using different viral proteins. However, the mechanisms are not fully elucidated. In this study, we demonstrated that the nonstructural protein 2 (NS2) of H1N1 IAV negatively regulate the induction of type-I interferon. Co-immunoprecipitation experiments revealed that NS2 specifically interacts with interferon regulatory factor 7 (IRF7). NS2 blocks the nuclear translocation of IRF7 by inhibiting the formation of IRF7 dimers, thereby prevents the activation of IRF7 and inhibits the production of interferon-beta. Taken together, these findings revealed a novel mechanism by which the NS2 of H1N1 IAV inhibits IRF7-mediated type-I interferon production.

摘要

甲型流感病毒(IAV)是一种在全球范围内传播的人畜共患病病原体,可导致人和动物发生高度传染性呼吸道疾病,具有高发病率和死亡率。IAV 进化出了多种策略来对抗先天免疫反应,利用不同的病毒蛋白。然而,这些机制尚未完全阐明。在本研究中,我们证明了 H1N1 IAV 的非结构蛋白 2(NS2)负调控 I 型干扰素的诱导。免疫共沉淀实验表明,NS2 特异性地与干扰素调节因子 7(IRF7)相互作用。NS2 通过抑制 IRF7 二聚体的形成来阻止 IRF7 的核易位,从而阻止 IRF7 的激活并抑制干扰素-β的产生。综上所述,这些发现揭示了 H1N1 IAV 的 NS2 抑制 IRF7 介导的 I 型干扰素产生的新机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ecb/9694023/a27a5b71d115/viruses-14-02411-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ecb/9694023/17321666e811/viruses-14-02411-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ecb/9694023/868b37917934/viruses-14-02411-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ecb/9694023/03ba93f0ba5b/viruses-14-02411-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ecb/9694023/a54a2607000f/viruses-14-02411-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ecb/9694023/a27a5b71d115/viruses-14-02411-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ecb/9694023/17321666e811/viruses-14-02411-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ecb/9694023/868b37917934/viruses-14-02411-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ecb/9694023/03ba93f0ba5b/viruses-14-02411-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ecb/9694023/a54a2607000f/viruses-14-02411-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ecb/9694023/a27a5b71d115/viruses-14-02411-g005.jpg

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