Short STIM1 isoform attenuates STING-IFN signaling pathway to facilitate ranavirus infection

Stromal interaction molecule 1 (STIM1) is recognized as a key calcium sensor involved in store-operated calcium entry, playing a crucial role in the regulation of the host innate immune responses. Recently, a short isoform of mammalian STIM1 was identified, which replaces intact STIM1 for calcium transport. However, the functions of short isoform in innate immune responses remains unclear. In this study, the role of the short isoform of STIM1 ( sc STIM1s) in regulating the stimulator of interferon genes (STING) in the interferon pathway and its impact on viral replication were investigated in a teleost fish Siniperca chuatsi (mandarin fish). We found that sc STIM1s share similar domains with the STIM1 protein but lacks the Pro/Ser-rich region and Poly-K domain at the C-terminus. The sc STIM1s gene was widely expressed in the immune tissues and responded to mandarin fish ranavirus (MRV) infection suggesting sc STIM1s might be involved in the immune response. Our results show that sc STIM1s interacted with STING and attenuated STING-mediated interferon signaling to facilitate MRV replication. These findings were the first to demonstrate a role of the short isoform of STIM1 in the regulation of innate immunity and enhances the understanding of the immune system in teleost fish to facilitate the prevention and control of aquatic viral diseases.