Anatid herpesvirus 1 US10 recruits TRIM13 to ubiquitinate STING for autophagic degradation and immune suppression

The innate immune response is central to antiviral defense, and viruses have evolved sophisticated evasion strategies. Anatid Herpesvirus 1 (AnHV-1) is a pathogenic alphaherpesvirus causing immunosuppression with economic and biosecurity impacts, yet its evasion of immune signaling pathways remains poorly understood. Here we show that AnHV-1 tegument protein US10 suppresses innate immunity by targeting stimulator of interferon genes (STING) for autophagosome-lysosome degradation. US10 associates with STING and binds the autophagy-related protein microtubule-associated protein 1 light chain 3 beta (LC3B), enhancing delivery to lysosomes. Mechanistically, US10 recruits E3 ligase tripartite motif-containing protein 13 (TRIM13) and induces stress in the endoplasmic reticulum through the Protein kinase R-like Reticulum Kinase (PERK). These synergistic actions inhibit type I interferon (IFN-I) production and IFN-stimulated gene expression. Deletion of US10 reduces viral replication and pathogenicity while enhancing immune activation in cells and animals. Our findings uncover a dual autophagy-based mechanism of immune evasion and highlight potential therapeutic targets against AnHV-1 and related alphaherpesviruses.