Pigeon employs a conserved IRF7 gene to mediate innate immune response.

Compared with chickens and ducks, pigeons exhibit higher resistance to RNA virus infection. Interferon regulatory factor 7 (IRF7) was identified a member of the interferon regulatory factors (IRFs) family, which plays an important role in innate immune response. Subsequent studies have shown that IRF7 performs a diverse function in multiple biological processes. In this study, pigeon IRF7 (piIRF7) was first cloned, and bioinformatics analysis showed that IRF7 varies among species, but the IRF and IRF3 domains are highly conserved. Further study showed that only NDV infection upregulated IRF7 mRNA levels in vivo, and NDV, AIV, FPV infection, and nucleic acids mimic stimulation also significantly upregulated piIRF7 mRNA levels in PEFs. Furthermore, overexpressing piIRF7 promoted IFNs and IFN-stimulated genes (ISGs) activation and inhibited NDV and VSV replication. Importantly, we observed that pigeon and chicken IRF7 suppressed viral replication more efficiently than human and bat IRF7 in IRF7KO DF-1 cells. Structurally, we discovered that the IRF domain of piIRF7 is indispensable for IFN-β activation. This study provides data to identify the function of piIRF7 and to better understand antiviral innate immunity in pigeons.