Yin Mengge, Li Xiangmin, Zhang Min, Zhao Qiongqiong, Wang Haoyuan, Zhang Huiyan, Lu Zengjun, Qian Ping
National Key Laboratory of Agricultural Microbiology, Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan, 430070, Hubei, China.
College of Veterinary Medicine, Huazhong Agricultural University. Wuhan, Hubei, 430070, China.
Vet Res. 2025 Apr 30;56(1):96. doi: 10.1186/s13567-025-01521-z.
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.
宿主细胞膜相关的RING-CH8蛋白（MARCH8）通过靶向病毒包膜糖蛋白发挥抗病毒宿主因子的作用。口蹄疫病毒（FMDV）是一种无包膜的正链单链RNA病毒。MARCH8对FMDV复制的潜在影响仍不确定。在此，我们发现MARCH8的过表达以剂量依赖性方式显著抑制FMDV复制。相反，MARCH8的敲低促进了FMDV复制。具体而言，MARCH8与VP1、VP2和VP3相互作用，以蛋白酶体依赖性方式介导它们的降解。MARCH8催化VP1、VP2和VP3的K33连接的多聚泛素化。此外，VP1的Lys210残基、VP2的Lys63残基和VP3的Lys118残基被确定为MARCH8介导降解的关键靶位点。总体而言，我们得出结论，MARCH8是一种针对FMDV的内在抗病毒因子。
