非洲猪瘟病毒E248R蛋白抑制cGAS-STING介导的天然免疫

The E248R protein of African swine fever virus inhibits the cGAS-STING-mediated innate immunity

摘要:

为了探究ASFV E248R蛋白调控cGAS-STING信号通路的机制，利用双荧光素酶报告系统验证ASFV E248R蛋白够剂量依赖性地抑制cGAS-STING和HT-DNA诱导的IFN-β的产生。通过相对定量PCR技术验证，过表达E248R抑制IFNB1、RANTES、IL-6和TNF-αb基因的转录水平。免疫共沉淀和激光共聚焦试验结果表明，E248R与STING相互作用。通过蛋白印迹试验证实，过表达E248R可抑制STING的表达。研究表明ASFV E248R蛋白通过抑制STING的表达拮抗天然免疫应答。该结果将扩展对ASF免疫逃逸的认知，为疫苗的研制提供新的思路。

Abstract:

We researched the mechanism of African swine fever virus (ASFV) protein E248R in regulating the cGAS-STING pathway. First, we verified via the dual-luciferase reporter assay system that E248R protein inhibited the secretion of IFN-β induced by cGAS-STING or HT-DNA in a dose-dependent manner. The relative quantitative PCR analysis indicated that the overexpression of E248R inhibited HT-DNA-induced transcription of IFN-b1, RANTES, IL-6, and TNF-α in PK-15 cells. Next, we found that E248R interacted with STING by co-immunoprecipitation assay and laser confocal microscopy. Finally, we demonstrated that E248R inhibited the expression of STING protein by using Western blotting. We demonstrated for the first time that the E248R protein of ASFV suppressed the host innate immune response via inhibiting STING expression. The results are pivotal in extending the understanding of the ASFV immune escape and can guide the design of vaccines against ASFV.