Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China; Gembloux Agro-bio Tech, University of Liège, Liège, 4000, Belgium.
Biochem Biophys Res Commun. 2018 Nov 30;506(3):437-443. doi: 10.1016/j.bbrc.2018.10.103. Epub 2018 Oct 20.
African swine fever virus (ASFV) is a highly pathogenic large DNA virus that causes African swine fever (ASF) in domestic pigs and European wild boars with mortality rate up to 100%. The DP96R gene of ASFV encodes one of the viral virulence factors, yet its action mechanism remains unknown. In this study, we report that DP96R of ASFV China 2018/1 strain subverts type I IFN production in cGAS sensing pathway. DP96R inhibited the cGAS/STING, and TBK1 but not IRF3-5D mediated IFN-β and ISRE promoters activation. Furthermore, DP96R selectively blocked the activation of NF-κB promoter induced by cGAS/STING, TBK1, and IKKβ, but not by overexpression of p65. Moreover, DP96R inhibited phosphorylation of TBK1 stimulated by cGAS/STING activation, and TBK1-induced antiviral response. Finally, truncated mutation analysis demonstrated that the region spanning amino acids 30 to 96 of DP96R was responsible for the inhibitory activity. To our knowledge, this is for the first time that DP96R of ASFV China 2018/1 is reported to negatively regulate type I IFN expression and NF-κB signaling by inhibiting both TBK1 and IKKβ, which plays an important role in virus immune evasion.
非洲猪瘟病毒（ASFV）是一种高致病性的大型 DNA 病毒，可导致家猪和欧洲野猪发生非洲猪瘟（ASF），死亡率高达 100%。ASFV 的 DP96R 基因编码一种病毒毒力因子，但它的作用机制尚不清楚。在本研究中，我们报告称，ASFV 中国 2018/1 株的 DP96R 可破坏 cGAS 感应途径中的 I 型 IFN 产生。DP96R 抑制了 cGAS/STING 和 TBK1，但不抑制 IRF3-5D 介导的 IFN-β和 ISRE 启动子激活。此外，DP96R 选择性地阻断了 cGAS/STING、TBK1 和 IKKβ诱导的 NF-κB 启动子的激活，但不阻断 p65 的过表达。此外，DP96R 抑制了 cGAS/STING 激活刺激的 TBK1 的磷酸化，以及 TBK1 诱导的抗病毒反应。最后，截断突变分析表明，DP96R 中 30 至 96 个氨基酸的区域负责抑制活性。据我们所知，这是首次报道 ASFV 中国 2018/1 株的 DP96R 通过抑制 TBK1 和 IKKβ负调控 I 型 IFN 表达和 NF-κB 信号通路，这在病毒免疫逃避中发挥重要作用。
