数字农科院2.0

Quantitative proteomic analysis identifies the unfolded protein response as a host pathway co-opted by ASFV to promote replication

文献类型： 外文期刊

作者： Zhang, Danyang;Liu, Baohong;Liu, Huanan;Mao, Ruoqing;Cao, Weijun;Zhang, Xiangle;Yang, Fayu;Wang, Yichao;Shen, Chaochao;Zhang, Shilei;Zhu, Zixiang;Zheng, Haixue

作者机构：

关键词： African swine fever virus;proteomics;unfolded protein response;replication

期刊名称： MBIO

ISSN：

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 a highly contagious disease that affects pigs, resulting in substantial economic losses in the global pig industry. A comprehensive understanding of viral-host protein interactions can facilitate the discovery of therapies for viral infection. In this study, we employ a 4D label-free quantitative proteomics approach to profile a comprehensive protein dynamics analysis in ASFV-infected pigs, identifying over 6,000 proteins across multiple organs. Our results reveal coordinated interorgan responses characterized by inflammatory activation and interferon signaling in defense against ASFV. The protein-protein interaction network analysis uncovers ASFV-induced functional modules, including the unfolded protein response (UPR), innate immune signaling, and inflammation, which are conserved across tissues. Notably, ASFV robustly activates all three branches of the UPR both in vivo and in vitro to promote viral replication. Furthermore, we identify that the virus-encoded protein D117L interacts with multiple UPR-related host proteins, thereby directly triggering UPR activation. Collectively, this study delineates the organ-specific proteomic landscape of ASFV infection, providing valuable insights into virus-host interactions and offering potential therapeutic targets for ASF.IMPORTANCEAfrican swine fever virus (ASFV) has caused severe consequences for the global pig industry. In this study, we conducted a multi-organ proteomic analysis using a 4D label-free quantitative proteomics approach and mapped the organ-specific proteomic landscape during ASFV infection. This work overcomes the limitations of most existing studies, which are primarily restricted to in vitro cell models and provide a more comprehensive understanding of ASFV infection and pathogenesis. Notably, the viral D117L protein is identified as a critical modulator of host cellular responses, directly subverting the unfolded protein response (UPR) pathway through specific interactions with host UPR-associated proteins. Collectively, our work lays the foundation for understanding the pathogenesis of ASFV, providing potential therapeutic strategies against African swine fever.

分类号：

  • 相关文献

[1]Research progress on the proteins involved in African swine fever virus infection and replication. Xianghan Duan,Yi Ru,Wenping Yang,Jingjing Ren,Rongzeng Hao,Xiaodong Qin,Dan Li,Haixue Zheng. 2022

[2]The CP123L protein of African swine fever virus is a membrane-associated, palmitoylated protein required for viral replication. Guan, Xiangyu,Wang, Tao,Gao, Yuxuan,Zhai, Huanjie,Jiang, Fengwei,Hou, Qinghe,Yang, Xiaoke,Wu, Hongxia,Li, Lian-Feng,Luo, Yuzi,Li, Su,Sun, Yuan,Qiu, Hua-Ji,Li, Yongfeng. 2025

[3]Synergistic effect of the responses of different tissues against African swine fever virus. Fan, Wenhui,Cao, Ying,Jiao, Pengtao,Yu, Ping,Zhang, He,Chen, Teng,Zhou, Xintao,Qi, Yu,Sun, Lei,Liu, Di,Zhu, Hongfei,Liu, Wenjun,Hu, Rongliang,Li, Jing. 2021

[4]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

[5]Regulation of Stress Responses and Translational Control by Coronavirus. Fung, To Sing,Liu, Ding Xiang,Liao, Ying. 2016

[6]Acute heat stress alters the expression of genes and proteins associated with the unfolded protein response pathway in the liver of broilers. Miao, Q. X.,Si, X. Y.,Xie, Y. J.,Chen, L.,Tang, X. F.,Zhang, H. F.. 2021

[7]The Regulation of Integrated Stress Response Signaling Pathway on Viral Infection and Viral Antagonism. Yongshu Wu,Zhidong Zhang,Yanmin Li,Yijing Li. 2022

[8]Mycoplasma hyopneumoniae membrane protein Mhp271 interacts with host UPR protein GRP78 to facilitate infection. Pan, Qiao,Xu, Qingyuan,Liu, Tong,Zhang, Yujuan,Xin, Jiuqing. 2022

[9]Mycoplasma hyopneumoniae inhibits the unfolded protein response to prevent host macrophage apoptosis and M2 polarization. Liu, Tong,Zhang, Yujuan,Zhao, Huanjun,Wu, Qi,Xin, Jiuqing,Pan, Qiao. 2024

[10]Geminivirus βV1- protein activates bZIP17/28mediated UPR signaling to facilitate viral pathogenicity but its activity is attenuated by autophagic degradation in plants. Hu, Tao,Li, Chenyang,Liu, Hui,Su, Chenlu,Wang, Yaqin,Li, Fangfang,Zhou, Xueping. 2025

[11]HAX1 mediates SARS-CoV-2 spike-triggered unfolded protein response in host cells. Zhu, Fang,Sheng, Xiangpeng,Yang, Fan,Wang, Xuechen,Yang, Cong,Ren, Jin,Wang, Chengcheng,Hu, Ronggui. 2025

[12]Manipulation of the Unfolded Protein Response by Intracellular Bacterial Pathogens: Mechanisms of ER Hijacking and Therapeutic Implications. Enhui Dai,Dongjie Sun,Yanxiao Zhao,Mengtao Zhang,Yifan Wu,Jiabo Ding. 2026

[13]The bZIP transcription factor RISBZ1 balances grain filling and ER stress response in rice grains. Qi Sun,Erchao Duan,Ruonan Jing,Yulong Ren,Huan Xu,Chuanwei Gu,Wenting Lv,Xiaokang Jiang,Rongbo Chen,Qingkai Wang,Yipeng Zhang,Rushuang Zhang,Hongyi Xu,Yunpeng Zhang,Jiajia Chi,Yunfei Fu,Yun Zhu,Yu Zhang,Binglei Zhang,Xuan Teng,Hui Dong,Xue Yang,Lei Zhou,Yunlu Tian,Xi Liu,Shijia Liu,Xiuping Guo,Cailin Lei,Ling Jiang,Yihua Wang,Jianmin Wan. 2025

[14]C-terminal truncation of the transmembrane protein of an attenuated lentiviral vaccine alters its in vitro but not in vivo replication and weakens its potential pathogenicity. Jiang, Cheng-Gang,Gao, Xu,Ma, Jian,Lin, Yue-Zhi,Wang, Xue-Feng,Zhao, Li-Ping,Zhou, Jian-Hua,Jiang, Cheng-Gang,Liu, Di,Hua, Yue-Ping,Gao, Xu. 2011

[15]Newcastle disease virus induces stable formation of bona fide stress granules to facilitate viral replication through manipulating host protein translation. Sun, Yingjie,Dong, Luna,Yu, Shengqing,Wang, Xiaoxu,Zheng, Hang,Zhang, Pin,Meng, Chunchun,Zhan, Yuan,Tan, Lei,Song, Cuiping,Qiu, Xusheng,Liao, Ying,Ding, Chan,Dong, Luna,Zheng, Hang,Wang, Xiaoxu,Wang, Guijun,Ding, Chan.

[16]Mutational analysis of the SDD sequence motif of a PRRSV RNA-dependent RNA polymerase. Zhou Yan,Zheng HaiHong,Gao Fei,Tian DeBin,Yuan ShiShan. 2011

[17]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.

[18]Effect of ORF119 gene deletion on the replication and virulence of orf virus. Qiao, J.,Yang, H. B.,Peng, Y. L.,Meng, Q. L.,Chen, C.,Ma, Y.,Xie, K.,Liu, T. L.,Chen, C. F.,Cai, X. P..

[19]Cysteine residues of the porcine reproductive and respiratory syndrome virus ORF5a protein are not essential for virus viability. Sun, Lichang,Zhou, Yan,Liu, Runxia,Li, Yanhua,Gao, Fei,Wang, Xiaomin,Yuan, Shishan,Wei, Zuzhang,Tong, Guangzhi,Fan, Hongjie,Wei, Zuzhang.

[20]Exchange of the VP5 of infectious bursal disease virus in a serotype I strain with that of a serotype II strain reduced the viral replication and cytotoxicity. Qin, Liting,Qi, Xiaole,Gao, Honglei,Gao, Yulong,Bu, Zhigao,Wang, Xiaomei. 2009

作者其他论文 更多>>