SADS-CoV NS3 induces apoptosis by blocking the formation of Bcl-xL-BAK complex

Swine acute diarrhea syndrome coronavirus (SADS-CoV) has caused significant disruptions in porcine breeding and raised concerns regarding potential human infection. Thus far, the roles of virus proteins in virus replication and pathogenesis remain largely unknown. Here, we first investigated the functions of SADS-CoV NS3 in apoptosis and viral pathogenicity. Our findings indicated that NS3 blocked the combination of anti-apoptosis protein Bcl-xL with pro-apoptosis protein BAK, then promoting the BAK pore-forming and inducing mitochondrion-mediated apoptosis, thereby enhancing the pathogenicity of virus. Moreover, we also discovered for the first time that Bcl-xL could act as an important antiviral factor to inhibit SADS-CoV replication. These results contribute valuable insights into the novel roles of bat-borne coronavirus accessory proteins in viral replication and pathogenicity in potentially infected hosts.