Caprine Kobuvirus VP1 Protein Activates the Mitochondrial Apoptotic Pathway via Interaction with BAD

Caprine kobuvirus (CKoV) is a member of the Picornaviridae family that causes enteritis in goats and poses a significant health threat, yet its molecular pathogenesis remains largely unknown. Here, we show that experimental infection of goats with CKoV induces apoptosis in the spleen, lungs, and intestine tissues. In vitro, CKoV infection of HEK293T cells triggers apoptosis, with the viral structural protein VP1 identified as sufficient to induce apoptosis. VP1 activates the mitochondrial (intrinsic) apoptotic pathway, as evidenced by increased reactive oxygen species (ROS) production, activation of caspase-9 and caspase-3, elevated Bax/Bcl-2 ratio, cytochrome c release, and Bax translocation to mitochondria. Notably, VP1 associates with the pro-apoptotic protein BAD (BCL2-associated agonist of cell death) and co-localizes with it in mitochondria. Overexpression of BAD enhances VP1-induced apoptosis, whereas BAD knockdown by siRNA suppresses it, demonstrating that BAD plays a contributory role in VP1-induced apoptosis. These findings uncover a novel VP1-BAD mitochondrial apoptosis axis in CKoV pathogenesis and suggest that VP1 may merit further investigation as a potential molecular target for antiviral intervention against CKoV-associated enteritis in goats.