H5N1亚型禽流感病毒PB2蛋白与MAVS蛋白相互作用而抑制鸭β干扰素信号通路

doi:10.1016/j.jia.2023.12.040

Journal of Integrative Agriculture ›› 2025, Vol. 24 ›› Issue (9): 3614-3625.DOI: 10.1016/j.jia.2023.12.040

H5N1亚型禽流感病毒PB2蛋白与MAVS蛋白相互作用而抑制鸭β干扰素信号通路

收稿日期:2023-10-08 修回日期:2024-01-03 接受日期:2023-12-01 出版日期:2025-09-20 发布日期:2025-08-11

H5N1 avian influenza virus PB2 antagonizes duck IFN-β signaling pathway by targeting mitochondrial antiviral signaling protein

Zuxian Chen^{1, 3}, Bingbing Zhao^{1, 2}, Yingying Wang¹, Yuqing Du¹, Siyu Feng¹, Junsheng Zhang¹, Luxiang Zhao¹, Weiqiang Li¹, Yangbao Ding¹, Peirong Jiao^{1, 3#}

¹College of Veterinary Medicine/Guangdong Laboratory for Lingnan Modern Agriculture, South China Agricultural University, Guangzhou 510642, China
²State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, China
³Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, Guangzhou 510642, China

Received:2023-10-08 Revised:2024-01-03 Accepted:2023-12-01 Online:2025-09-20 Published:2025-08-11
About author:Zuxian Chen, E-mail: czx0216@outlook.com; #Correspondence Peirong Jiao, Tel: +86-20-85280234, E-mail: prjiao@scau.edu.cn
Supported by:
This work was supported by the grants from the National Natural Science Foundation of China (31872497 and 32072844), the National Key Research and Development Program of China (2021YFD1800200 and 2016YFD0500207), and the Laboratory of Lingnan Modern Agriculture Project, China (NT2021007).

摘要/Abstract

摘要：

禽流感（Avian influenza）是由禽流感病毒（avian influenza virus，AIV）引起鸡、鸭等多种家禽及野鸟感染或患病的一种高度接触性传染病。某些禽流感病毒可导致人类和其他哺乳动物患病或亚临床感染。因此，禽流感严重危害家禽业，并严重威胁人类健康。I型干扰素（interferon，IFN）介导的天然免疫反应是宿主抵御病毒感染的第一道防线。然而，禽流感病毒抑制鸭I型干扰素产生的分子机制仍不完全清楚。在本研究中，为验证鸭MAVS蛋白的功能，首先在鸭成纤维细胞（duck embryo fibroblast，DEF）中过表达鸭MAVS基因及其各结构域的基因片段。通过荧光定量的方法发现，鸭MAVS基因可使其下游基因TRAF3、IRF7、IFN-β和炎症细胞因子IL-6的mRNA表达量明显上调；荧光素酶报告基因分析发现，鸭MAVS蛋白能显著激活禽IFN-β和禽IRF7启动子的活性。因此，鸭MAVS蛋白正调控鸭I型干扰素信号通路。进一步实验发现，H5N1亚型高致病性禽流感病毒的聚合酶碱性蛋白2（polymerase basic 2，PB2）与鸭线粒体抗病毒蛋白（mitochondrial antiviral signaling protein，MAVS）相互作用，进而抑制鸭I型干扰素信号通路。免疫共沉淀实验发现，H5N1亚型禽流感病毒PB2蛋白与鸭MAVS蛋白的△TM结构域相互作用；H5N1流感病毒PB2蛋白的PB1结合结构域（PB1 binding domain，PBD）和RNA结合核输入结构域（RNA binding nuclear import domain，RND）是其与鸭MAVS蛋白相互作用的关键区域。另外，H5N1流感病毒PB2蛋白的PB1结合结构域和RNA结合核输入结构域是抑制鸭MAVS蛋白介导的I型干扰素信号通路的关键区域。综上所述，H5N1亚型禽流感病毒PB2蛋白与鸭MAVS蛋白相互作用，进而负调控鸭RLR（retinoic acid-inducible gene I (RIG-I)-like receptor，RLR）信号通路中MAVS蛋白介导的抗病毒天然免疫反应。本研究有助于了解禽流感病毒蛋白调控RLR信号通路以逃逸鸭宿主抗病毒天然免疫反应的分子机制。

Abstract:

Type I interferon (IFN)-mediated innate immune responses represent the first line of host defense against viral infection. However, the molecular mechanisms by which avian influenza virus (AIV) inhibits type I IFN production in ducks are not well understood. Here, we first found that the polymerase basic 2 (PB2) protein of H5N1 subtype AIV inhibited the type I IFN responses by targeting duck mitochondrial antiviral signaling protein (MAVS). We further demonstrated that H5N1-PB2 bound to the Δtransmembrane (ΔTM) domain of duck MAVS, and the polymerase basic 1 (PB1) binding domain (PBD) and RNA binding nuclear import domain (RND) of H5N1-PB2 interacted with MAVS to inhibit type I IFN expression in ducks. Collectively, our findings contribute to understanding the molecular mechanism by which AIV proteins regulate the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) signaling pathway to evade host antiviral immune responses in ducks.

Key words: avian influenza virus , polymerase basic 2 , mitochondrial antiviral signaling protein , duck , type I interferon

Zuxian Chen, Bingbing Zhao, Yingying Wang, Yuqing Du, Siyu Feng, Junsheng Zhang, Luxiang Zhao, Weiqiang Li, Yangbao Ding, Peirong Jiao. H5N1亚型禽流感病毒PB2蛋白与MAVS蛋白相互作用而抑制鸭β干扰素信号通路[J]. Journal of Integrative Agriculture, 2025, 24(9): 3614-3625.

Zuxian Chen, Bingbing Zhao, Yingying Wang, Yuqing Du, Siyu Feng, Junsheng Zhang, Luxiang Zhao, Weiqiang Li, Yangbao Ding, Peirong Jiao. H5N1 avian influenza virus PB2 antagonizes duck IFN-β signaling pathway by targeting mitochondrial antiviral signaling protein[J]. Journal of Integrative Agriculture, 2025, 24(9): 3614-3625.

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H5N1亚型禽流感病毒PB2蛋白与MAVS蛋白相互作用而抑制鸭β干扰素信号通路

H5N1 avian influenza virus PB2 antagonizes duck IFN-β signaling pathway by targeting mitochondrial antiviral signaling protein

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