lncRNA ch-MYC-AS1 restricts ALV-J replication by disrupting the ANXA2-C-Myc oncogenic axis

The c-Myc oncogene is a critical regulator of viral oncogenesis and immune evasion in multiple cancers. However, its modulation by long noncoding RNAs (lncRNAs) during retroviral infection remains poorly understood. Here, we show that ch-MYC-AS1, a novel lncRNA, restricts avian leukosis virus subgroup J (ALV-J) replication by targeting c-Myc protein expression using chicken macrophage HD11 cells. Mechanistically, ch-MYC-AS1 binds to annexin A2 (ANXA2) and impedes its nuclear translocation, preventing its collaboration with c-Myc to promote glycolysis. This dual inhibition suppresses c-Myc-driven metabolic reprogramming essential for viral proliferation. Our findings reveal ch-MYC-AS1 as a key suppressor of retroviral replication through coordinated disruption of c-Myc/ANXA2 signaling, providing a potential therapeutic strategy for antiviral and anticancer drug development.IMPORTANCEAvian leukosis virus subgroup J (ALV-J) is an oncogenic retrovirus that causes tumors and immunosuppression in chickens, leading to significant economic losses in poultry industries. This study identifies a host-derived long noncoding RNA (lncRNA), ch-MYC-AS1, which suppresses ALV-J replication by disrupting the ANXA2-c-Myc signaling axis. These findings unveil a novel layer of antiviral defense mediated by an epigenetically regulated lncRNA and highlight a potential RNA-based strategy to combat retroviral infections. Moreover, targeting the ANXA2-c-Myc interaction may offer therapeutic insights for controlling ALV-J and other MYC-driven diseases.