Zhang Ruinan, Wang Mingshu, Cheng Anchun, Yang Qiao, Ou Xumin, Sun Di, Tian Bin, He Yu, Wu Zhen, Huang Juan, Wu Ying, Zhang Shaqiu, Zhao Xinxin, Yu Yanling, Zhang Ling, Zhu Dekang, Jia Renyong, Chen Shun, Liu Mafeng
Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Chengdu 611130, China.; College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu 611130, China; Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the People's Republic of China, Chengdu 611130, China.
Institute of Veterinary Medicine and Immunology, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Chengdu 611130, China.; College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu 611130, China; Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the People's Republic of China, Chengdu 611130, China..
Int J Biol Macromol. 2025 Feb;291:139040. doi: 10.1016/j.ijbiomac.2024.139040. Epub 2024 Dec 23.
The picornavirus 3C protein plays a crucial role in viral infection. One of its functions is inhibiting the immune response by cleaving or degrading innate immune-related proteins to promote viral infection. Annexin A2 (ANXA2) is a multifunctional host protein that plays a key role in various cellular processes, it also participates in viral infection. However, whether the ANXA2 protein interacts with the picornavirus 3C protein to regulate viral infection and its effect on type I interferon (IFN) has not been reported. In this study, we found that the 3C protein of duck hepatitis A virus 1 (DHAV-1) interacts with the ANXA2 protein and upregulates ANXA2 expression. Moreover, the ANXA2 protein interacts with the cGAS, STING, RIG-I, MDA5, MAVS, and TBK1 proteins, suppresses its activated IFN-β and ISRE promoter activity, promotes RIG-I, MDA5, and TBK1 protein degradation through caspase-dependent pathway, thereby inhibiting IFN-β production and promoting DHAV-1 proliferation. This study lays a theoretical foundation for further understanding the interaction between viruses and hosts, as well as for analyzing the function of the picornavirus 3C protein and the ANXA2 protein. It also suggests a novel pathway, such as targeting key sites on the 3C protein to upregulate ANXA2, for a target-based antiviral strategy.
微小核糖核酸病毒3C蛋白在病毒感染中起关键作用。其功能之一是通过切割或降解天然免疫相关蛋白来抑制免疫反应，以促进病毒感染。膜联蛋白A2（ANXA2）是一种多功能宿主蛋白，在各种细胞过程中起关键作用，它也参与病毒感染。然而，ANXA2蛋白是否与微小核糖核酸病毒3C蛋白相互作用以调节病毒感染及其对I型干扰素（IFN）的影响尚未见报道。在本研究中，我们发现鸭甲型肝炎病毒1型（DHAV-1）的3C蛋白与ANXA2蛋白相互作用并上调ANXA2表达。此外，ANXA2蛋白与cGAS、STING、RIG-I、MDA5、MAVS和TBK1蛋白相互作用，抑制其激活的IFN-β和ISRE启动子活性，通过半胱天冬酶依赖性途径促进RIG-I、MDA5和TBK1蛋白降解，从而抑制IFN-β产生并促进DHAV-1增殖。本研究为进一步了解病毒与宿主之间的相互作用以及分析微小核糖核酸病毒3C蛋白和ANXA2蛋白的功能奠定了理论基础。它还提出了一种新的途径，如靶向3C蛋白上的关键位点以上调ANXA2，用于基于靶点的抗病毒策略。
