MARCH2 inhibits avian leukosis virus replication by targeting gp85 for ubiquitination and degradation
文献类型: 外文期刊
作者: Yuntong Chen;Longbo Wu;Wenrui Fan;Ying Wang;Jinglei Li;Xuefu Zhang;Zibo Zhang;Yumeng Li;Suyan Wang;Yongzhen Liu;Xiaole Qi;Yanping Zhang;Hongyu Cui;Yulu Duan;Yulong Gao
作者机构:
关键词: ubiquitination; degradation; gp85; MARCH2; avian leukosis virus
期刊名称: Journal of Virology
ISSN: 0022-538X
年卷期: 2025 年
页码:
收录情况: SCIE(2025版)
摘要: The replication of avian leukosis virus (ALV), a simple retrovirus that induces neoplastic diseases in chickens, is regulated by host factors. Investigating the antiviral activity of these host factors and the underlying mechanisms could provide a theoretical foundation for the prevention and control of ALV infections. In this study, RNA sequencing revealed that ALV-A infection upregulates the expression of membrane-associated RING-CH 2 (MARCH2). Increasing MARCH2 levels inhibited ALV-A replication by 3.47- to 16.98-fold in viral titer, while conversely, knockout of MARCH2 promoted it by 5.04- to 10.70-fold. MARCH2 was found to interact with the viral gp85 protein, catalyzing its K27-linked ubiquitination and proteasomal degradation at lysine 282 (K282). Substituting K282 with arginine prevented degradation and enhanced ALV-A replication. Importantly, the K282 site was determined to be conserved across various ALV subgroups, with its mutation disrupting MARCH2-mediated degradation. Our findings not only identified MARCH2 as a robust defense mechanism against multiple ALV subgroups, functioning by targeting viral proteins, but also provide a potential target for novel strategies against avian leukosis.
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