MARCH2 inhibits avian leukosis virus replication by targeting gp85 for ubiquitination and degradation

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 · 发表于：Journal of Virology · 年份：2025 · DOI：10.1128/jvi.01616-25 · 被引用次数：2 · 研究领域：Herpesvirus Infections and Treatments、interferon and immune responses、T-cell and Retrovirus Studies

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.IMPORTANCEAvian leukosis virus (ALV), a simple retrovirus, not only causes chicken tumor disease and immunosuppression but, more importantly, can spread vertically through hatching eggs, affecting the quality of chicks and endangering the safety of poultry breeds. Currently, no v...