PCSK9 potentiates innate immune response to RNA viruses by preventing AIP4-mediated polyubiquitination and degradation of VISA/MAVS
文献类型： 外文期刊
作者： Fang, Han 1 ; Shi, Mengling 1 ; Wang, Cong 1 ; Zhang, Saiting 1 ; Kong, Na 1 ; Ji, Mengyao 3 ; Wang, Yan 2 ; Zhou, Yidan 4 ; Zhu, Qiyun 1 ; Zhang, Yu 1 ; Du, Shishen 2 ; Xu, Shuai 3 ; Lei, Caoqi 1 ;
作者机构： 1.Wuhan Univ, Coll Life Sci, Frontier Sci Ctr Immunol & Metab, State Key Lab Virol & Biosafety, Wuhan 430072, Hubei, Peoples R China
2.Wuhan Univ, Coll Life Sci, Hubei Key Lab Cell Homeostasis, Wuhan 430072, Hubei, Peoples R China
3.Chinese Acad Agr Sci, Lanzhou Vet Res Inst, State Key Lab Anim Dis Prevent & Control, Lanzhou 730000, Peoples R China
4.Wuhan Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Wuhan 430071, Peoples R China
5.Lanzhou Univ, Sch Basic Med Sci, Lanzhou 730000, Peoples R China
关键词： VISA/MAVS; innate immune response; PCSK9; interferon
期刊名称：PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA （ 影响因子：9.1； 五年影响因子：10.6 ）
ISSN： 0027-8424
年卷期： 2025 年 122 卷 8 期
页码：
收录情况： SCI
摘要： Upon viral infection, retinoic acid- inducible gene- I (RIG- I)- like receptors (RLRs) detect viral RNA to initiate antiviral innate immune response, which is mediated by the mitochondrial adaptor protein VISA virus- induced signaling adaptor; also known as mitochondiral antiviral- signaling protein (MAVS). The stability and activity of VISA are tightly regulated by various posttranslational modifications, among which polyubiquitination plays important roles. Various E3 ubiquitin ligases, including atrophin interacting protein 4 (AIP4), mediate polyubiquitination of VISA and result in its degradation. However, how polyubiquitination of VISA is regulated remains unclear. Here, we uncovered a dual function for proprotein convertase subtilisin/kexin type 9 (PCSK9), a key enzyme in cholesterol homeostasis and a well- known therapeutic target in cardiovascular diseases, modulating host responses to RNA viruses both extracellularly and intracellularly. Secreted PCSK9 inhibited sendai virus (SeV) and vesicular stomatitis virus (VSV) infection, while the intracellular PCSK9 potentiated RLRs- mediated interferons (IFNs) induction by stabilizing VISA on mitochondria. Viral infection induced the translocation of PCSK9 to mitochondria where it competed with AIP4 for VISA, thereby inhibiting its polyubiquitination and degradation. Consequently, overexpression of PCSK9 enhanced VISA- mediated innate immune response against RNA viral infection, whereas its deficiency had the opposite effects and resulted in more robust replication of the virus. Pcsk9-/- mice produced lower levels of type I IFNs and proinflammatory cytokines, rendering the increased sensitivity to VSV and influenza A virus infection. Altogether, our findings uncovered an important and unexpected role of PCSK9 in virus-host interaction and contribute to the understanding of the sophisticated mechanism governing the proper and efficient immune response to viral infection.
- 相关文献
作者其他论文 更多>>
-
Mitigating greenhouse gases and ammonia emission from the storage of digested pig slurry: Adaption of dissolved oxygen
作者：Cao, Tiantian;Zheng, Yunhao;Wang, Shunli;Zhu, Zhiping;Chen, Yongxing;Wang, Yue;Dong, Hongmin;Cao, Tiantian;Zheng, Yunhao;Wang, Shunli;Zhu, Zhiping;Chen, Yongxing;Wang, Yue;Dong, Hongmin;Zhang, Yu;Guo, Dongpo
关键词：Biogas digestate; Dissolved oxygen; GHG reduction; Ammonia reduction
-
Salmonella Typhimurium persistently infects host via its effector SseJ-induced PHB2-mediated mitophagy
作者：Sun, Dage;Li, Jiayi;Dai, Changzhi;Chen, Kaifeng;Wang, Yu;Pan, Peng;Zhu, Ting;Xu, Chenggang;Liao, Ming;Zhang, Jianmin;Gou, Hongchao;Shen, Haiyan;Zhang, Yu;Shan, Tongling;Liao, Ming
关键词：Mitophagy; PHB2; PINK1; PRKN;
Salmonella Typhimurium; SseJ -
Advances in molecular epidemiology and detection methods of pseudorabies virus
作者：Zhuang, Linlin;Yang, Jianbo;Liu, Qingxin;Shen, Qiuping;Zhuang, Linlin;Zhao, Ying;Zhang, Yu;Zhuang, Linlin;Zhao, Ying;Zhang, Yu;Gong, Jiansen;Shen, Jingyi
关键词：Pseudorabies virus; Epidemiology; Vaccines; Molecular detection methods
-
Genome-Wide Identification and Analysis of Carbohydrate-Binding Modules in Colletotrichum graminicola
作者：Wang, Ya-Fei;Huang, Qiu-Li;Li, Hong-Lian;Chang, Jia-Xin;Zhang, Yu;Wang, Yi-Wen;Shi, Yan;Chen, Xin-Yu
关键词：
Colletotrichum graminicola ; carbohydrate-binding modules; gene family; expression pattern -
BTG3 inhibits porcine epidemic diarrhea virus replication by promoting viral S2 protein degradation through the autophagy and proteasome pathways
作者：Zhu, Qingxiao;Liu, Xuelan;Kong, Ning;Zhu, Qingxiao;Liu, Tian;Qin, Wenzhen;Yang, Xinyu;Tong, Wu;Yu, Hai;Zheng, Hao;Tong, Guangzhi;Shan, Tongling;Kong, Ning;Shan, Tongling;Kong, Ning;Zhang, Yu
关键词：BTG3; PEDV S2 subunit; Degradation; Autophagy pathway
-
Efficacy of Chlorogenic Acid in Treating Tripterygium Glycoside-Induced Asthenozoospermia in Rats and Its Possible Mechanisms
作者：Chen, Long;Bello-Onaghise, God'spower;Li, Shunda;Zhang, Yu;Qu, Qianwei;Li, Yanhua;Bello-Onaghise, God'spower;Chen, Mo;Wang, Haoran
关键词：Tripterygium glucosides; asthenozoospermia; chlorogenic acid; antioxidants; oxidative stress; network pharmacology
-
Bacterial communities driving cabbage yield increases and pathogenic risks reduces following wastewater irrigation: Effects of nitrification inhibitors on different soil-vegetable systems
作者：Zhang, Manyun;Zhou, Minzhe;Wang, Hua;Ma, Bin;Zhou, Tangrong;Wang, Yan;Huang, Zhenrong;Tang, Wenhui;Chen, Falin;Zhao, Xinlin;Zhang, Manyun;Bai, Shahla Hosseini;Zhao, Benliang
关键词：Nitrification inhibitors; Rice-fish symbiosis wastewater; Potential pathogenicity; Bacterial community
