Seneca Valley virus 3C protease targets TRIM32 for cleavage to antagonize its antiviral effects

Seneca Valley virus (SVV) is an emerging pathogen that causes vesicular diseases in pigs, posing a significant threat to the global swine industry. Tripartite motif-containing protein (TRIM) family members are recognized as intrinsic antiviral effectors that provide a frontline shield against viruses prior to the transcription of interferon (IFN) and interferon-stimulated genes (ISGs). In this study, we uncovered the antiviral mechanism, which promotes the K48-linked ubiquitination of viral VP3 protein, leading to the degradation of VP3 via the proteasome pathway. SVV 3C^pro abolished the antiviral effects of TRIM32 by inducing its cleavage. The cleaved TRIM32 fragment attenuates its E3 ubiquitin ligase activity and weakens the activation of IFN signaling. Our results reveal a potential mechanism of viral immune evasion, which is crucial for understanding how SVV has evolved a novel strategy to evade the intrinsic cellular restrictions against viral infection.