Chicken infectious anemia virus exploits host CK2α as an essential factor for its replication via VP2 Ser182/Asp183-mediated interaction

. Our results indicate that CIAV exploits cellular CK2α for its replication and pathogenesis, implying that CK2α can be used as a potential target for the development of antiviral drugs in effective control of CIAV infection. IMPORTANCE: Chicken infectious anemia virus (CIAV) causes severe immunosuppression and substantial economic losses in the global poultry industry. Current strategies to control CIAV infection are still limited. This study identifies host kinase casein kinase 2 alpha (CK2α) as a key cellular factor that binds and stabilizes CIAV VP2, promoting viral replication. Inhibition or knockdown of CK2α suppressed viral replication. The rescued virus with VP2 S182A/D183A mutations exhibited reduced viral replication and attenuated pathogenicity. These findings reveal a crucial mechanism whereby CIAV VP2 exploits host CK2α for efficient viral replication, highlighting the VP2-CK2α interaction as a potential target for developing novel antiviral strategies.