The Seneca Valley virus 3C protease cleaves DCP1A to attenuate its antiviral effects.

Abstract

Seneca Valley virus (SVV), a new member of Picornaviridae, causes idiopathic vesicular symptoms in pregnant sows and acute death in neonatal piglets, considerably damaging the swine industry. The viral protease 3C (3C^pro) cleaves host immune-related molecules to create a favorable environment for viral replication. In this study, we found that mRNA decapping enzyme 1A (DCP1A) is a novel antiviral effector against SVV infection that targets 3D viral RNA-dependent RNA polymerase for OPTN-mediated autophagic degradation. To counteract this effect, SVV 3C^pro targets DCP1A for cleavage at glutamine 343 (Q343), resulting in the cleaved products DCP1A (1-343) and DCP1A (344-580), which lose the ability to restrict SVV replication. In contrast, the 3C cleavage-resistant DCP1A-Q343A mutant exhibited stronger antiviral effects than the wild-type DCP1A. Additionally, the degradation of the viral 3D protein targeted by DCP1A was abolished after its cleavage by SVV 3C^pro. In conclusion, our study demonstrated that SVV 3C^pro is a pivotal ISG antagonist that cleaves DCP1A. These results offer novel insight into how viruses evade host immunity.