Avian leukosis virus subgroup J evades innate immunity by activating miR-155 to dually target TRAF3 and STAT1.

• Published in: PLoS Pathogens
• Main Authors: Xinyue Zhang, Defang Zhou, Jing Zhou, Xiaoyang Liu, Longying Ding, Tianxing Yan, Mengyuan Shi, Shuhai He, Ziqiang Cheng
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2025-10-01
• Online Access: https://doi.org/10.1371/journal.ppat.1013552

Avian leukosis virus subgroup J (ALV-J) causes immunosuppression and myelocytomas in poultry. While ALV-J evades innate immunity to sustain infection, the mechanisms remain unclear. Here, we show that ALV-J upregulates microRNA-155 (miR-155) to suppress type I interferon (IFN-I) responses, facilitating viral replication. Mechanistically, the ALV-J p27 protein reduced DEAD-box helicase 3X (DDX3X) promoter activity, repressing its expression and promoting MIR155 host gene (MIR155HG) processing into mature miR-155. miR-155 directly targets the tumor necrosis factor receptor-associated factor 3 (TRAF3) and the signal transducer and activator of transcription 1 (STAT1), both of which are key regulators of IFN-I response. Silencing TRAF3 or STAT1 rescues ALV-J replication suppressed by miR-155 inhibition. These findings reveal a novel miRNA-mediated innate immune evasion strategy employed by ALV-J, enhancing our understanding of retroviral pathogenesis.