Senecavirus A 2B protein suppresses type I interferon production by inducing the degradation of MAVS

文献类型： 外文期刊

第一作者： Liu, Huanan

作者： Liu, Huanan;Li, Kangli;Chen, Wenzhe;Yang, Fan;Cao, Weijun;Zhang, Keshan;Li, Pengfei;Zhu, Zixiang;Zheng, Haixue;Liu, Huanan;Tang, Lijie

作者机构：

关键词： Senecavirus A; 2B protein; MAVS; Type I interferon; Innate immune response

期刊名称：MOLECULAR IMMUNOLOGY （ 影响因子：4.174； 五年影响因子：4.24 ）

ISSN： 0161-5890

年卷期： 2022 年 142 卷

页码：

收录情况： SCI

摘要： Senecavirus 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.

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