Duck plague virus ICP27 protein suppresses IFN-β production by dual targeting of DNA- and RNA-sensing pathways.

Duck plague virus (DPV), an alphaherpesvirus causing severe economic losses in global waterfowl industries, adopts sophisticated strategies to subvert host antiviral immunity. Here, we identify DPV ICP27 as a pivotal immune evasion protein that concurrently inhibits both DNA (cGAS-STING) and RNA (RIG-I/MDA5-MAVS) innate immune sensing pathways-a novel function unreported in avian herpesviruses. Through co-transfection and infection assays in duck embryo fibroblasts (DEFs), we demonstrate that ICP27 suppresses key immune sensors' transcriptional and protein expression levels (STING, RIG-I) and the transcription factor IRF7. Co-immunoprecipitation confirms ICP27 binds to IRF7, impairing interferon regulatory functions, impairing interferon regulatory functions. Crucially, infection with ICP27-knockout DPV (DPV-ΔICP27) significantly enhances IFN-β, IL-6, Mx, and OASL expression compared to wild-type virus. Phylogenetic analyses reveal conserved yet species-specific functional divergence of ICP27 across herpesviruses. Our findings identify a unique "multi-target cooperative suppression" mechanism employed by DPV, which enhances our understanding of avian herpesviral immune evasion and offers potential targets for developing novel antiviral strategies.