数字农科院2.0

MARCH8 inhibits pseudorabies virus replication by trapping the viral cell-to-cell fusion complex in the trans-Golgi network

文献类型： 外文期刊

作者： Cui Hong Rao;Rui Huang;Yuan Zhe Bai;Changqing Yu;Meng Chen;Jin Mei Peng;Shi Jia Xu;Ming Xia Sun;Shu Jie Wang;Yong Bo Yang;Tong Qing An;Zhi Jun Tian;Chuang Lyu;Xue Hui Cai;Chunfu Zheng;Fandan Meng;Yan Dong Tang

作者机构：

关键词： Cell-to-cell fusion;MARCH8;TGN

期刊名称： International Journal of Biological Macromolecules

ISSN： 0141-8130

年卷期： 2024 年 274 卷

页码：

收录情况： SCIE（2024版） ; ; EI（2024版）

摘要： The membrane-associated RING-CH 8 protein (MARCH8), a member of the E3 ubiquitin ligase family, has broad-spectrum antiviral activity. However, some viruses hijack MARCH8 to promote virus replication, highlighting its dual role in the viral lifecycle. Most studies on MARCH8 have focused on RNA viruses, leaving its role in DNA viruses largely unexplored. Pseudorabies virus (PRV) is a large DNA virus that poses a potential threat to humans. In this study, we found that MARCH8 inhibited PRV replication at the cell-to-cell fusion stage. Interestingly, our findings proved that MARCH8 blocks gB cleavage by recruiting furin but this activity does not inhibit viral infection in vitro. Furthermore, we confirmed that MARCH8 inhibits cell-to-cell fusion independent of its E3 ubiquitin ligase activity but dependent on the interaction with the cell-to-cell fusion complex (gB, gD, gH, and gL). Finally, we discovered that the distribution of the cell-to-cell fusion complex is significantly altered and trapped within the trans-Golgi network. Overall, our results indicate that human MARCH8 acts as a potent antiviral host factor against PRV via trapping the cell-to-cell fusion complex in the trans-Golgi network.

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