Abstract
Chicken infectious anemia virus (CIAV) induces severe immunosuppression in chickens. The nonstructural protein VP2 of CIAV is shown to play critical roles in viral assembly and viral replication. However, the molecular mechanisms by which CIAV VP2 hijacks host machinery to promote efficient viral replication remain elusive. Here, we showed that casein kinase 2 alpha (CK2α) subunit was identified to interact with CIAV VP2 to promote viral replication. We found that knockdown of cellular CK2α by RNAi in MDCC-MSB1 or inhibition of its kinase activity by an inhibitor significantly suppressed CIAV replication in cells. Furthermore, we verified that CK2α stabilized VP2 by inhibiting its proteasomal degradation. In addition, we demonstrated that Ser182 and Asp183 of VP2 served as essential residues for CK2α binding. Using reverse genetics technique, we rescued the recombinant virus with mutations at Ser182 and Asp183 of VP2 and demonstrated that mutations at these sites disrupted VP2-CK2α binding, reduced viral replication, and mitigated CIAV-induced bone marrow hypoplasia and thymic damage in vivo. 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.