MARCH8 promotes the proteasomal degradation of foot-and-mouth disease virus VP1, VP2, and VP3 to negatively regulate viral replication
文献类型： 外文期刊
作者： Yin, Mengge 1 ; Li, Xiangmin 1 ; Zhang, Min 1 ; Zhao, Qiongqiong 1 ; Wang, Haoyuan 1 ; Zhang, Huiyan 6 ; Lu, Zengjun 6 ; Qian, Ping 1 ;
作者机构： 1.Huazhong Agr Univ, Natl Key Lab Agr Microbiol, Hubei Hongshan Lab, Wuhan 430070, Hubei, Peoples R China
2.Huazhong Agr Univ Wuhan, Coll Vet Med, Wuhan 430070, Hubei, Peoples R China
3.Cooperat Innovat Ctr Sustainable Pig Prod, Key Lab Prevent Vet Med Hubei Prov, Wuhan 430070, Hubei, Peoples R China
4.Minist Agr Peoples Republ China, Key Lab Dev Vet Diagnost Prod, Wuhan 430070, Hubei, Peoples R China
5.Hubei Jiangxia Lab, Wuhan 430200, Peoples R China
6.Chinese Acad Agr Sci, Lanzhou Vet Res Inst, State Key Lab Anim Dis Control & Prevent, Natl Foot and Mouth Dis Reference Lab, Lanzhou 730046, Gansu, Peoples R China
关键词： Membrane-associated RING-CH8 protein; foot-and-mouth disease virus; restriction factor; proteasomal degradation; K33-linked polyubiquitination
期刊名称：VETERINARY RESEARCH （ 影响因子：3.5； 五年影响因子：4.0 ）
ISSN： 0928-4249
年卷期： 2025 年 56 卷 1 期
页码：
收录情况： SCI
摘要： The host cell membrane-associated RING-CH8 protein (MARCH8) functions as an antiviral host factor by targeting viral envelope glycoproteins. Foot-and-mouth disease virus (FMDV) is a non-enveloped, positive-sense, single-stranded RNA virus. The potential impact of MARCH8 on FMDV replication remains uncertain. Here, we found that the overexpression of MARCH8 significantly inhibited FMDV replication in a dose-dependent manner. Conversely, the knockdown of MARCH8 facilitated FMDV replication. Specifically, MARCH8 interacted with VP1, VP2, and VP3, mediating their degradation in a proteasome-dependent manner. MARCH8 catalyzed the K33-linked polyubiquitination of VP1, VP2, and VP3. Moreover, the Lys210 residue of VP1, the Lys63 residue of VP2, and the Lys118 residue of VP3 were identified as critical target sites for MARCH8-mediated degradation. Overall, we conclude that MARCH8 is an intrinsic antiviral factor against FMDV.
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