Chicken infectious anemia virus (CIAV) VP1 antagonizes type I interferon (IFN-I) production by inhibiting TBK1 phosphorylation.

• CIAV VP1 protein inhibits IFN-I expression induced by cGAS-STING signaling. • VP1 inhibits TBK1 phosphorylation. • The 121–150 aa in VP1 is essential for VP1 to interact with TBK1 and inhibit cGAS-STING signaling. Chicken infectious anemia virus (CIAV) infection induces immunosuppression or subclinical immunosuppression in chickens. CIAV infection has been reported to repress type I interferon (IFN-I) expression, but the underlying mechanisms are not yet understood. Here we reported that VP1, the capsid protein of CIAV, the major immunogenic protein that triggers the production of neutralizing antibodies in chickens, inhibited type I interferon (IFN-I) expression induced by cGAS-STING signaling. We showed that VP1 inhibited TBK1 phosphorylation and down stream signal transduction, leading to the inhibition of IFN-I expression. Subsequently, we demonstrated that VP1 interacted with TBK1. Finally, we clarified that aa 120–150 in VP1 was essential for VP1 to interact with TBK1 and inhibit cGAS-STING signaling. These findings will help us further understand the pathogenesis of CIAV in chickens. [ABSTRACT FROM AUTHOR]