Black carp STAT2 inhibits IRF7-mediated antiviral response by altering its ubiquitination and nuclear transfer

Interferon regulatory factor 7 (IRF7) is a transcription factor induced by viral infection, playing a critical role in type I interferon (IFN-I) production and the establishment of an antiviral state. However, the regulatory mechanisms underlying piscine IRF7 remain largely uncharacterized. In this study, we demonstrate that the signal transducer and activator of transcription 2 (bcSTAT2) from black carp (Mylopharyngodon piceus) functions as a negative regulator of black carp IRF7 (bcIRF7)-mediated IFN signaling. Overexpressed bcSTAT2 significantly suppressed the induced IFN promoter transcription mediated by MDA5, MAVS, STING, TBK1, and IRF7 in reporter assays. We further identified the interaction and overlapping subcellular localization between bcSTAT2 and bcIRF7. Functionally, the association of these two molecules leads to the suppression of bcIRF7-triggered IFN production and antiviral responses, ultimately facilitating viral replication. Mechanistically, bcSTAT2 exerts this inhibitory effect by reducing K48- and K63-linked ubiquitination and enhancing K6- and K27-linked ubiquitination of bcIRF7, and impeding its nuclear translocation. Collectively, these findings offer novel insights into the regulation of antiviral IFN signaling in fish.