Abstract
? 2021 Elsevier LtdSenecavirus A (SVA) is an oncolytic virus, which can propagate in human tumor cells and has been used as an oncolytic virotherapy candidate in humans. Besides, SVA circulates in pigs and causes vesicles and coalescing erosions on the snouts and coronary bands in infected pigs and results in neonatal morbidity. SVA has evolved the ability to suppress host innate immune response to benefit viral replication. SVA 3Cpro and 2C protein inhibit the production of host type I interferon (IFN) by degradation of several components of innate immune pathway. In this study, for the first time, we determined that SVA 2B antagonized host innate immune response in both human and porcine cells. SVA 2B protein degraded mitochondrial antiviral-signaling protein (MAVS), a key host molecule in the innate immune pathway, and a colocalization and interaction between 2B and MAVS was observed in the context of viral infection. Further study showed that the 1-48 and 100-128 regions of 2B were essential for inhibition of type I IFN expression. In addition, we determined that 2B degraded MAVS depending on caspase-9 and caspase-3. In conclusion, our results revealed a novel strategy for SVA 2B protein to antagonize host innate immune response, which will help for clarification of the pathogenesis of SVA and provide an insight for oncolytic virotherapy of SVA.
NSTL
Elsevier