Chicken IRF10 suppresses the cGAS-STING-IFN antiviral signaling pathway by targeting IRF7

The chicken (ch) innate immune cGAS-STING-IFN signaling pathway plays a crucial role in host antiviral defense, wherein chIRF7 serves as the key downstream transcription factor of chSTING responsible for initiating type I IFN transcription. While chicken IRF family encompasses 8 members, the potential involvement of other IRF members in chicken cGAS-STING-IFN signaling transduction and/or regulation remains poorly characterized. In this study, we identified chIRF10 as a potent suppressor of chicken cGAS-STING-IFN signaling against several viruses, by screening of chIRF family members. Mechanistically, the inhibitory activity of chIRF10 depended on its IRF associated domain (IAD) but not its DNA binding domain (DBD). Further, chIRF10 suppressed both cGAS-STING mediated IFN signaling and TBK1/IKKε/IRF7 activated IFN signaling. Importantly, chIRF10 could interact with chIRF7, and inhibit its dimerization and activation. In summary, our findings unveiled a novel function of chIRF10 as well as a novel regulatory mechanism governing chicken cGAS-STING-IFN antiviral signaling, thereby providing a scientific foundation for developing strategies against chicken viral diseases.