数字农科院2.0

The African swine fever virus gene MGF_360-4L inhibits interferon signaling by recruiting mitochondrial selective autophagy receptor SQSTM1 degrading MDA5 antagonizing innate immune responses

文献类型： 外文期刊

作者： Sun, Hualin;Yang, Jifei;Zhang, Zhonghui;Wu, Mengli;Tian, Zhancheng;Liu, Ying;Zhang, Xiaoqiang;Zhong, Jianhao;Yang, Songlin;Chen, Yikang;Luo, Jianxun;Guan, Guiquan;Yin, Hong;Niu, Qingli

作者机构：

关键词： ASFV;MGF_360-4L;SQSTM1;MDA5;mitochondrial autophagy

期刊名称： MBIO

ISSN：

年卷期： 2025 年

页码：

收录情况： SCIE（2025版）

摘要： Multigene family (MGF) 360 genes, which are African swine fever virus (ASFV) virulence genes, primarily target key host immune molecules to suppress host interferon (IFN) production and interferon-stimulated gene (ISG) transcription, impairing host innate immune responses for efficient viral replication. However, the interactions between MGF 360 virulence genes and host molecules, as well as the mechanisms through which MGF 360 genes regulate host immune responses and IFN signaling, require further elucidation. In this study, we discovered that ASFV MGF_360-4L interacts with MDA5 and recruits the mitochondrial selective autophagy receptor SQSTM1 to degrade MDA5, thus impairing IFN signaling and compromising host innate immune responses. Furthermore, MGF_360-4L inhibits the interaction between MDA5 and MAVS, blocking ISG15-mediated ISGylation of MDA5. MGF_360-4L deficiency signifi cantly attenuated virus-induced mitochondrial autophagy in vitro. Additionally, OAS1 ubiquitinates MGF_360-4L at residues K290, K295, and K327. Finally, a recombinant ASFV lacking the MGF_360-4L gene (ASFV-triangle MGF_360-4L) was generated using ASFV-CN/SC/ 2019 as the backbone, which demonstrated that the replication kinetics of ASFV triangle MGF_360-4L in PAM cells were like those of the highly virulent parental ASFV-WT in vitro. Domestic pigs infected with ASFV-triangle MGF_360-4L exhibited milder symptoms than those infected with parental ASFV-WT, and ASFV-triangle MGF_360-4L-infected pigs presented with enhanced host innate antiviral immune response, confirming that the deletion of the MGF_360-4L gene from the ASFV genome highly attenuated virulence in pigs and provided effective protection against parental ASFV challenge. In conclusion, we identified a novel ASFV virulence gene, MGF_360-4L, further elucidating ASFV infection mechanisms and providing a new candidate for vaccine development.

分类号：

  • 相关文献

[1]ASFV毒力基因MGF-360-4L通过选择性自噬受体SQSTM1降解MDA5损害宿主天然免疫反应. 《中国兽医科学》编辑部,牛庆丽. 2025

[2]细胞内模式识别受体研究进展. 闫鸿斌,高闪电,贾万忠,才学鹏. 2008

[3]猪黑色素瘤分化相关基因5(MDA5)对口蹄疫病毒感染宿主的影响. 常兴妮,崔晓蕊,孙鹏,马凯凯,胡高维,杨建设,丁艳平,李志勇. 2017

[4]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

[5]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

[6]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

[7]Lgp2 Plays A Critical Role In Mda5-Mediated Antiviral Activity Against Duck Enteritis Virus. Huo, H, Zhao, LL, Wang, DF, Chen, XH, Chen, HY. 2019

[8]New role of gramicidin A in RIG-I-like receptors-mediated IFN signalling. Li, Xiao,Sun, Xinyuan,Yan, Zhongyi,Zhao, Zhenxiang,Pang, Zhaojun,Yang, Han,Ji, Xiaoxin,Lei, Yi,Zhu, Zixiang,Guo, Xiangqian,Mu, Xin. 2023

[9]Peste des Petits Ruminants Virus Upregulates STING to Activate ATF6-Mediated Autophagy. Zhang, Rui,Lin, Hanrui,You, Qing,Zhang, Zhixiong,Bai, Ling,Chen, Fei,Zhu, Xueliang,Zhang, Zhidong,Li, Yanmin. 2022

[10]Type I Interferon Induced And A.ntagonized By Foot-And-Mouth Disease V irus. Ma, XX,Ma, LN,Chang, QY,Ma, P,Li, LJ,Wang, YY,Ma, ZR,Cao, X. 2018

[11]RNF144B negatively regulates antiviral immunity by targeting MDA5 for autophagic degradation. Li, Guoxiu,Zhang, Jing,Zhao, Zhixun,Wang, Jian,Li, Jiaoyang,Xu, Weihong,Cui, Zhanding,Sun, Pu,Yuan, Hong,Wang, Tao,Li, Kun,Bai, Xingwen,Ma, Xueqing,Li, Pinghua,Fu, Yuanfang,Cao, Yimei,Bao, Huifang,Li, Dong,Liu, Zaixin,Zhu, Ning,Tang, Lijie,Lu, Zengjun. 2024

[12]Annexin A2 negatively regulates IFN-β production through targeting the RLR signaling pathway. Liu, Hongyang,Xue, Mengdi,Feng, Chunying,Yu, Jimin,Ye, Guangqiang,Zhang, Kunli,Huang, Li,Weng, Changjiang. 2026

[13]The integrin protein ITGβ1 effectively suppresses porcine epidemic diarrhea virus replication through facilitating MDA5 oligomerization and subsequent activation of the type I interferon signaling pathway. Yu, Jiarong,Sun, Qi,Zhu, Junrui,Cui, Yuxi,Chen, Pengfei,Shen, Wei,Yue, Ying,Jiang, Yifeng,Liu, Changlong,Liu, Huili,Tong, Guangzhi,Gao, Fei,Zhou, Yanjun. 2025

[14]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

[15]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

[16]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

[17]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

[18]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

[19]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

[20]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

作者其他论文 更多>>