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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： Rao, Cui-Hong 1 ; Huang, Rui 1 ; Bai, Yuan-Zhe 1 ; Yu, Changqing 2 ; Chen, Meng 1 ; Peng, Jin-Mei 1 ; Xu, Shi-Jia 1 ; Sun, Ming-Xia 1 ; Wang, Shu-Jie 1 ; Yang, Yong-Bo 1 ; An, Tong-Qing 1 ; Tian, Zhi-Jun 1 ; Lyu, Chuang 1 ; Cai, Xue-Hui 1 ; Zheng, Chunfu 6 ; Meng, Fandan 1 ; Tang, Yan-Dong 1 ;

作者机构： 1.Chinese Acad Agr Sci, Harbin Vet Res Inst, State Key Lab Vet Biotechnol, Harbin 150001, Peoples R China

2.Yibin Vocat & Tech Coll, Engn Ctr Agr Biosafety Assessment & Biotechnol, Sch Adv Agr Sci, Yibin, Peoples R China

3.Heilongjiang Prov Res Ctr Vet Biomed, Harbin, Peoples R China

4.Heilongjiang Prov Key Lab Vet Immunol, Harbin, Peoples R China

5.Qingdao Jiazhi Biotechnol Co Ltd, Qingdao Key Lab Livestock & Poultry Pathogen Biote, Qingdao 266100, Peoples R China

6.Univ Calgary, Dept Microbiol Immunol & Infect Dis, Calgary, AB, Canada

关键词： MARCH8; Cell-to-cell fusion; TGN

期刊名称：INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES （ 影响因子：7.7； 五年影响因子：7.7 ）

ISSN： 0141-8130

年卷期： 2024 年 274 卷

页码：

收录情况： SCI

摘要： The membrane-associated RING-CH 8 protein (MARCH8), a member of the E3 ubiquitin ligase family, has broadspectrum 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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