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

Autor: Rao CH; State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, China., Huang R; State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, China., Bai YZ; State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, China., Yu C; Engineering Center of Agricultural Biosafety Assessment and Biotechnology, School of Advanced Agricultural Sciences, Yibin Vocational and Technical College, Yibin, China., Chen M; State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, China., Peng JM; State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, China., Xu SJ; State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, China., Sun MX; State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, China; Heilongjiang Provincial Research Center for Veterinary Biomedicine, Harbin, China; Heilongjiang Provincial Key Laboratory of Veterinary Immunology, Harbin, China., Wang SJ; State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, China., Yang YB; State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, China., An TQ; State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, China., Tian ZJ; State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, China., Lyu C; State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, China; Qingdao Key Laboratory of Livestock & Poultry Pathogen Biotechnology, Qingdao Jiazhi Biotechnology Co., Ltd., Qingdao 266100, China., Cai XH; State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, China; Heilongjiang Provincial Research Center for Veterinary Biomedicine, Harbin, China., Zheng C; Department of Microbiology, Immunology & Infection Diseases, University of Calgary, Calgary, Alberta, Canada. Electronic address: zheng.alan@hotmail.com., Meng F; State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, China. Electronic address: mengfandan@caas.cn., Tang YD; State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, China; Heilongjiang Provincial Research Center for Veterinary Biomedicine, Harbin, China; Qingdao Key Laboratory of Livestock & Poultry Pathogen Biotechnology, Qingdao Jiazhi Biotechnology Co., Ltd., Qingdao 266100, China. Electronic address: tangyandong2008@163.com.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2024 Aug; Vol. 274 (Pt 2), pp. 133463. Date of Electronic Publication: 2024 Jun 27.
DOI: 10.1016/j.ijbiomac.2024.133463
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors declare no conflicts of interest.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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