数字农科院2.0

Picornavirus VP3 protein induces autophagy through the TP53-BAD-BAX axis to promote viral replication

文献类型： 外文期刊

作者： Mao, Ruoqing;Zhu, Zixiang;Yang, Fan;Sun, Dehui;Zhou, Xiaoli;Cao, Weijun;Qin, Xiaodong;Dang, Wen;Liu, Huanan;Tian, Hong;Zhang, Keshan;Wu, Qingfeng;Liu, Xiangtao;Zheng, Haixue

作者机构：

关键词： Autophagy;picornavirus;replication;TP53-BAD-BAX axis;VP3

期刊名称： AUTOPHAGY

ISSN： 1554-8627

年卷期： 2024 年

页码：

收录情况： SCIE（2024版）

摘要： Macroautophagy/autophagy and apoptosis are pivotal interconnected host cell responses to viral infection, including picornaviruses. Here, the VP3 proteins of picornaviruses were determined to trigger autophagy, with the autophagic flux being triggered by the TP53-BAD-BAX axis. Using foot-and-mouth disease virus (FMDV) as a model system, we unraveled a novel mechanism of how picornavirus hijacks autophagy to bolster viral replication and enhance pathogenesis. FMDV infection induced both autophagy and apoptosis in vivo and in vitro. FMDV VP3 protein facilitated the phosphorylation and translocation of TP53 from the nucleus into the mitochondria, resulting in BAD-mediated apoptosis and BECN1-mediated autophagy. The amino acid Gly129 in VP3 is essential for its interaction with TP53, and crucial for induction of autophagy and apoptosis. VP3-induced autophagy and apoptosis are both essential for FMDV replication, while, autophagy plays a more important role in VP3-mediated pathogenesis. Mutation of Gly129 to Ala129 in VP3 abrogated the autophagic regulatory function of VP3, which significantly decreased the viral replication and pathogenesis of FMDV. This suggested that VP3-induced autophagy benefits viral replication and pathogenesis. Importantly, this Gly is conserved and showed a common function in various picornaviruses. This study provides insight for developing broad-spectrum antivirals and genetic engineering attenuated vaccines against picornaviruses.Abbreviations: 3-MA, 3-methyladenine; ATG, autophagy related; BAD, BCL2 associated agonist of cell death; BAK1, BCL2 antagonist/killer 1; BAX, BCL2 associated X, apoptosis regulator; BBC3/PUMA, BCL2 binding component 3; BCL2, BCL2 apoptosis regulator; BID, BH3 interacting domain death agonist; BIP-V5, BAX inhibitor peptide V5; CFLAR/FLIP, CASP8 and FADD like apoptosis regulator; CPE, cytopathic effects; CQ, chloroquine; CV, coxsackievirus; DAPK, death associated protein kinase; DRAM, DNA damage regulated autophagy modulator; EV71, enterovirus 71; FMDV, foot-and-mouth disease virus; HAV, hepatitis A virus; KD, knockdown; MAP1LC3/LC3, microtubule associated protein 1 light chain 3; MOI, multiplicity of infection; MTOR, mechanistic target of rapamycin kinase; PML, promyelocytic leukemia; PV, poliovirus; SVA, Seneca Valley virus; TCID50, 50% tissue culture infectious doses; TOR, target of rapamycin. TP53/p53, tumor protein p53; WCL, whole-cell lysate.

分类号：

  • 相关文献

[1]Ribosomal protein L4 interacts with viral protein VP3 and regulates the replication of infectious bursal disease virus. Chen, Yuming,Lu, Zhen,Zhang, Lizhou,Gao, Li,Wang, Nian,Gao, Xiang,Wang, Yongqiang,Li, Kai,Gao, Yulong,Cui, Hongyu,Gao, Honglei,Liu, Changjun,Zhang, Yanping,Qi, Xiaole,Wang, Xiaomei,Wang, Xiaomei.

[2]Picornavirus VP2 protein suppresses innate immunity through selective autophagic degradation of IKBKE/IKKε. Li, Kangli,Zhang, Xiangle,Dong, Dandan,Zhu, Boning,Wang, Shuo,Wen, Xiaodan,Cao, Weijun,Ru, Yi,Tian, Hong,Zhu, Guoliang,He, Jijun,Guo, Jianhong,Dai, Jianye,Zheng, Haixue,Yang, Fan,Zhu, Zixiang. 2025

[3]Endoplasmic reticulum stress-mediated autophagy contributes to bluetongue virus infection via the PERK-eIF2 alpha pathway. Lv, Shuang,Sun, En-Cheng,Xu, Qing-Yuan,Zhang, Ji-Kai,Wu, Dong-Lai.

[4]Autophagy activated by duck enteritis virus infection positively affects its replication. Yin, Hai-Chang,Zhao, Li-Li,Niu, Yin-Jie,Lu, Tao-Feng,Han, Ling-Xia,Liu, Sheng-Wang,Chen, Hong-Yan,Li, Si-Qi,Jiang, Xin-Jie,Xu, Li-Jing.

[5]Autophagy Activated by Bluetongue Virus Infection Plays a Positive Role in Its Replication. Lv, Shuang,Xu, Qingyuan,Sun, Encheng,Yang, Tao,Li, Junping,Feng, Yufei,Zhang, Qin,Wang, Haixiu,Zhang, Jikai,Wu, Donglai. 2015

[6]Foot-And-Mouth Disease Virus Capsid Protein V.p2 Activates The Cellular E if2S1-Atf4 Pathway And Induces Autophagy Via Hspb1. Sun, P,Zhang, SM,Qin, XD,Chang, XN,Cui, XR,Li, HT,Zhang, SJ,Gao, HH,Wang, PH,Zhang, ZD,Luo, JX,Li, ZY. 2018

[7]Canine distemper virus N protein induces autophagy to facilitate viral replication. Fei Chen,Zijing Guo,Rui Zhang,Zhixiong Zhang,Bo Hu,Ling Bai,Shuaiyang Zhao,Yongshu Wu,Zhidong Zhang,Yanmin Li. 2023

[8]HACD3 Prevents PB1 from Autophagic Degradation to Facilitate the Replication of Influenza A Virus. Qibing Li,Li Jiang,Yihan Wang,Xuwei Liu,Bo Wang,Zhibo Shan,Yi Han Wang,Yuqin Wang,Hualan Chen,Chengjun Li. 2024

[9]猪繁殖与呼吸综合征病毒感染和复制机制及其毒力研究进展AdvancesinUnderstandingoftheInfection/ReplicationMechanismsandVirulenceDeterminantsofthePorcineReproductiveandRespiratorySyndromeVirus. 刘杏,王凤雪,温永俊*LIUXing,WANGFengxue,WENYongjun*. 2015

[10]口蹄疫病毒vp3-间接免疫荧光诊断方法的建立. 王冰,周国辉,涂亚斌,朴范泽,于力. 2008

[11]利用噬菌体随机肽库筛选传染性法氏囊病病毒VP3抗原表位. 邓小芸,高玉龙,高宏雷,祁小乐,程宇,王晓艳,王笑梅. 2006

[12]传染性法氏囊病毒结构蛋白基因VP3的克隆与原核表达. 彭志伟,王笑梅,高宏雷,付朝阳,张厚双,包晓玮,冉多良. 2005

[13]嵌合型口蹄疫病毒样颗粒构建、表达及鉴定. 刘绒欢,郭慧琛,杜平,董虎,郭梦楠,孙世琪. 2020

[14]新型鸭细小病毒VP3基因克隆与原核表达. 经美,王建昌,崔元,李晓轩,陈萍,王金凤,侯绍华,孙继国,袁万哲. 2018

[15]VP3 G–H环中氨基酸突变对O型口蹄疫病毒生物学特性的影响. 陈冬冬,白兴文,宫晓华,包慧芳,李平花,李冬,付元芳,白启峰,袁红,孙普,马雪青,曹轶梅,陈应理,卢曾军,刘在新. 2019

[16]Generation and evaluation of a recombinant genotype VII Newcastle disease virus expressing VP3 protein of Goose parvovirus as a bivalent vaccine in goslings. Wang, Jianzhong,Cong, Yanlong,Yin, Renfu,Ding, Zhuang,Wang, Jianzhong,Cong, Yanlong,Yin, Renfu,Ding, Zhuang,Wang, Chunfeng,Feng, Na,Yang, Songtao,Xia, Xianzhu,Xiao, Yueqiang,Wang, Wenxiu,Liu, Xiufan,Hu, Shunlin,Ding, Chan,Yu, Shengqing.

[17]Virus-like particles in picornavirus vaccine development. Dong, Hu,Guo, Hui-Chen,Sun, Shi-Qi.

[18]A single amino acid in the C-terminus of VP3 protein influences the replication of attenuated infectious bursal disease virus in vitro and in vivo. Wang, Yongqiang,Qi, Xiaole,Kang, Zhonghui,Yu, Fei,Qin, Liting,Gao, Honglei,Gao, Yulong,Wang, Xiaomei. 2010

[19]Antigenic structure analysis of VP3 of infectious bursal disease virus. Deng, Xiaoyun,Gao, Yulong,Gao, Honglei,Qi, Xiaole,Cheng, Yu,Wang, Xiaoyan,Wang, Xiaomei. 2007

[20]Structural diversity and biological role of the 5' untranslated regions of picornavirus. Peng, Tingyu,Yang, Fayu,Yang, Fan,Cao, Weijun,Zheng, Haixue,Zhu, Zixiang. 2023

作者其他论文 更多>>