The function of feline stimulator of interferon gene (STING) is evolutionarily conserved

•Feline STING shares the highest similarity with bovine STING.•Feline STING was also involved in type I IFN signaling.•The C-terminal tail of feline STING was necessary for the induction of IFN-β.•Feline STING activated the ISRE promoter.

Stimulator of interferon gene (STING) mediates the induction of type I IFN responses. In this study, feline STING was cloned. Full-length STING contains 1134 bp and encodes a 377 amino acid product that shares the highest similarity with bovine STING. STING is primarily expressed in the spleen, lungs and lymph nodes. An examination of its cellular localization indicated that STING is localized in the endoplasmic reticulum (ER) and contains two ER retention motifs, RPR and KKNF. Overexpressing STING induced the IFN response via the IRF3, NF-κB and AP-1 pathways. Moreover, the C-terminus of STING was required for the activation of IRF3 and AP-1. Knockdown of STING impaired the IFN-β response triggered by poly(dA:dT), poly(I:C) or SeV. Finally, STING activated the ISRE promoter and increased the expression of ISG15 and viperin. Collectively, our findings indicate that STING is involved in the regulation of the IFN-β pathway in felines.