数字农科院2.0

Role of g5Rp in African swine fever virus replication: disruption of host translation and autophagy

文献类型： 外文期刊

作者： Xu, Chunmei;Liang, Ruiying;Zhang, Yongqiang;Zhang, Xinyue;Zhang, Xiangyin;Luo, Xinru;Liu, Dahu;Hou, Shaohua;Ding, Jiabo;Tang, Xinming;Liang, Lin;Chang, Lingling;Li, Jinming;Weng, Changjiang;Wang, Zhiliang;Zhao, Xiaomin

作者机构：

关键词： ASFV;g5Rp;eIF5A;RPS15;9 ''-methyl salvianolate B

期刊名称： JOURNAL OF VIROLOGY

ISSN： 0022-538X

年卷期： 2025 年

页码：

收录情况： SCIE（2025版）

摘要： African swine fever (ASF), caused by the African swine fever virus (ASFV), is one of the most severe viral diseases affecting swine. ASFV employs sophisticated strategies to subvert host immune responses; however, the function of the viral protein g5Rp in viral pathogenesis remains incompletely defined. In this study, we demonstrate that g5Rp plays a critical role in viral replication by impairing host translation and autophagy. Overexpression of g5Rp enhanced viral replication and increased p30 protein levels, whereas siRNA-mediated knockdown of g5Rp suppressed both, underscoring its essential proviral function. Proteomic profiling of infected porcine macrophages (3D4/21 cells) revealed that g5Rp dysregulated 122 host proteins, predominantly involved in translation, autophagy, and apoptosis pathways. Mechanistically, g5Rp directly interacted with eIF5A and RPS15, disrupting their complex formation and thereby inhibiting translation initiation and autophagic flux. Structural analyses identified key residues (SER118, SER206, and ASN(61)) critical for this interference. Mutation of these residues abrogated g5Rp activity. Furthermore, virtual screening identified 9 ''-methyl salvianolate B as a potent g5Rp inhibitor, which restored eIF5A hypusination, promoted autophagy, and suppressed ASFV replication in vitro. Collectively, our findings establish g5Rp as a pivotal regulator of ASFV pathogenesis and a promising target for antiviral drug development.IMPORTANCEASFV has caused significant economic losses to the global pork industry, and no effective treatment or prevention currently exists. In this study, the interaction of g5Rp with the host proteins eIF5A and RPS15 was identified for the first time, and its crucial role in the viral life cycle was clarified. Resolving the crystal structure of g5Rp revealed its binding site to the host protein, which provides a new target for developing antiviral strategies against g5Rp. Additionally, the screened 9 ''-methyl salvianolate B, a small-molecule inhibitor, has shown the potential to effectively reduce viral replication and restore host protein synthesis. These findings not only deepen our understanding of the mechanism of ASFV infection but also lay the foundation for developing effective anti-ASFV treatment strategies in the future, which has important scientific implications.

分类号：

  • 相关文献

[1]兰花eIF5A基因家族鉴定与生物信息学分析. 张杰伟,汤久杨,陈兰芬,王宁琳,王宏芝,魏建华. 2017

[2]ASFV解旋酶D1133L蛋白表达和抗体检测方法的建立及初步应用. 侯景,申超超,张大俊,杨博,史喜绢,张婷,杨泽晓,张克山,郑海学,李丹,党文,刘湘涛. 2021

[3]非洲猪瘟病毒多基因家族MGF360-13L基因功能的初步研究. 陈达年,马旭升,代军飞,汪洋,李茜,白衡,毛甜甜,刘永生,丁龙,陈昊翰,陈思言,饶宇飞,贾宁,张杰,郑海学,刘湘涛. 2022

[4]非洲猪瘟病毒E184L蛋白的原核表达及单克隆抗体的制备. 李雪雯,李婷婷,李长尧,焦爽,郑君,荣俊,翁长江. 2023

[5]Deletion of African Swine Fever Virus (ASFV) H240R Gene Attenuates the Virulence of ASFV by Enhancing NLRP3-Mediated Inflammatory Responses. Huang, Li,Liu, Hongyang,Ye, Guangqiang,Liu, Xiaohong,Chen, Weiye,Wang, Zilong,Zhao, Dongming,Zhang, Zhaoxia,Feng, Chunying,Hu, Liang,Yu, Huibin,Zhou, Shijun,Zhang, Xianfeng,He, Xijun,Zheng, Jun,Bu, Zhigao,Li, Jiangnan,Weng, Changjiang. 2023

[6]Development of a new effective African swine fever virus vaccine candidate by deletion of the H240R and MGF505-7R genes results in protective immunity against the Eurasia strain. Li, Jiangnan,Song, Jie,Zhou, Shijun,Li, Shuai,Liu, Jia,Li, Tingting,Zhang, Zhaoxia,Zhang, Xianfeng,He, Xijun,Chen, Weiye,Zheng, Jun,Zhao, Dongming,Bu, Zhigao,Huang, Li,Weng, Changjiang. 2023

[7]African Swine Fever Virus H240R Protein Inhibits the Production of Type I Interferon through Disrupting the Oligomerization of STING. Ye, Guangqiang,Liu, Hongyang,Liu, Xiaohong,Chen, Weiye,Li, Jiangnan,Zhao, Dongming,Wang, Gang,Feng, Chunying,Zhang, Zhaoxia,Zhou, Qiongqiong,Zheng, Jun,Bu, Zhigao,Weng, Changjiang,Huang, Li. 2023

[8]African swine fever virus E120R protein inhibits interferon beta production by interacting with IRF3 to block its activation. Huisheng Liu,Zixiang Zhu,Tao Feng,Zhao Ma,Qiao Xue,Panxue Wu,Pan Li,Shasha Li,Fan Yang,Weijun Cao,Zhaoning Xue,Hongjun Chen,Xiangtao Liu,Haixue Zheng. 2021

[9]Development and in vivo evaluation of MGF100-1R deletion mutant in an African swine fever virus Chinese strain. Yingnan Liu,Yao Li,Zhenhua Xie,Qingying Ao,Dongdong Di,Wanqi Yu,Lu Lv,Qiuping Zhong,Yingying Song,Xinxin Liao,Qingqing Song,Heng Wang,Hongjun Chen. 2021

[10]Identification of one novel epitope targeting p54 protein of African swine fever virus using monoclonal antibody and development of a capable ELISA. Yunlei Cao,Dongmei Han,Yujiao Zhang,Kuan Zhang,Nannan Du,Wu Tong,Guoxin Li,Hao Zheng,Changlong Liu,Fei Gao,Guangzhi Tong. 2021

[11]Multifunctional pMGF505-7R Is a Key Virulence-Related Factor of African Swine Fever Virus. Li Huang,Jiangnan Li,Jun Zheng,Dan Li,Changjiang Weng. 2022

[12]African swine fever virus f317l protein inhibits nf-k b activation to evade host immune response and promote viral replication. Jinping Yang,Shasha Li,Tao Feng,Xiangle Zhang,Fan Yang,Weijun Cao,Hongjun Chen,Huisheng Liu,Keshan Zhang,Zixiang Zhu,Haixue Zheng. 2021

[13]Genome-wide transcriptomic analysis of highly virulent African swine fever virus infection reveals complex and unique virus host interaction. Xiaohui Ju,Fang Li,Jingrui Li,Chunyan Wu,Guangtao Xiang,Xiaomin Zhao,Yuchen Nan,Dongming Zhao,Qiang Ding. 2021

[14]Functional Analysis and Proteomics Profiling of Extracellular Vesicles From Swine Plasma Infected by African Swine Fever Virus. Guowei Xu,Xijuan Shi,Huanan Liu,Chaochao Shen,Bo Yang,Ting Zhang,Xuehui Chen,Dengshuai Zhao,Jinke Yang,Yu Hao,Huimei Cui,Xingguo Yuan,Xiangtao Liu,Keshan Zhang,Haixue Zheng. 2022

[15]The African swine fever virus protease pS273R inhibits DNA sensing cGAS-STING pathway by targeting IKKε. Jia Luo,Jiajia Zhang,Jinghua Ni,Sen Jiang,Nengwen Xia,Yiwen Guo,Qi Shao,Qi Cao,Wanglong Zheng,Nanhua Chen,Quan Zhang,Hongjun Chen,Qing Chen,Hongfei Zhu,François Meurens,Jianzhong Zhu. 2022

[16]A new B cell epitope of pC129R protein of African swine fever virus identified by monoclonal antibodies. Junrong Wang,Juan Bai,Lujie Zhang,Tingting Xia,Xing Yang,Keshan Zhang,Yanni Gao,Ping Jiang. 2023

[17]Sequential Deletions of Interferon Inhibitors MGF110-9L and MGF505-7R Result in Sterile Immunity against the Eurasia Strain of Africa Swine Fever. Ding, Mingyang,Dang, Wen,Liu, Huanan,Zhang, Keshan,Xu, Fan,Tian, Hong,Huang, Huaguo,Shi, Zhengwang,Sunkang, Yongjie,Qin, Xiaodong,Zhang, Yong,Zheng, Haixue. 2022

[18]An insight into the transmission role of insect vectors based on the examination of gene characteristics of African swine fever virus originated from non-blood sucking flies in pig farm environments. 安同庆. 2020

[19]Bayesian Phylodynamic Analysis Reveals the Dispersal Patterns of African Swine Fever Virus. Zhao Ji Shen,Hong Jia,Chun Di Xie,Jurmt Shagainar,Zheng Feng,Xiaodong Zhang,Kui Li,Rong Zhou. 2022

[20]African swine fever virus f317l protein inhibits nf-k b activation to evade host immune response and promote viral replication. Jinping Yang,Shasha Li,Tao Feng,Xiangle Zhang,Fan Yang,Weijun Cao,Hongjun Chen,Huisheng Liu,Keshan Zhang,Zixiang Zhu,Haixue Zheng. 2021

作者其他论文 更多>>