MARCH8 promotes the proteasomal degradation of foot-and-mouth disease virus VP1, VP2, and VP3 to negatively regulate viral replication

被引：0

作者：

Mengge Yin ^{[1
]}

Xiangmin Li ^{[2
]}

Min Zhang ^{[1
]}

Qiongqiong Zhao ^{[2
]}

Haoyuan Wang ^{[3
]}

Huiyan Zhang ^{[4
]}

Zengjun Lu ^{[5
]}

Ping Qian ^{[1
]}

机构：

[1] Huazhong Agricultural University,National Key Laboratory of Agricultural Microbiology, Hubei Hongshan Laboratory

[2] Huazhong Agricultural University. Wuhan,College of Veterinary Medicine

[3] The Cooperative Innovation Center for Sustainable Pig Production,Key Laboratory of Preventive Veterinary Medicine in Hubei Province

[4] Ministry of Agriculture of the People’s Republic of China,Key Laboratory of Development of Veterinary Diagnostic Products

[5] Hubei Jiangxia Laboratory,State Key Laboratory for Animal Disease Control and Prevention, National Foot

[6] Lanzhou Veterinary Research Institute,and

[7] Chinese Academy of Agricultural Sciences,Mouth Disease Reference Laboratory

来源：

Veterinary Research | / 56卷 / 1期

关键词：

Membrane-associated RING-CH8 protein; foot-and-mouth disease virus; restriction factor; proteasomal degradation; K33-linked polyubiquitination;

D O I：

10.1186/s13567-025-01521-z

中图分类号：

学科分类号：

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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