Deletion of MGF-110-9L gene from African swine fever virus weakens autophagic degradation of TBK1 as a mechanism for enhancing type I interferon production

文献类型： 外文期刊

第一作者： Ren, Jingjing

作者： Ren, Jingjing;Li, Dan;Zhu, Guoqiang;Yang, Wenping;Ru, Yi;Feng, Tao;Qin, Xiaodong;Hao, Rongzeng;Duan, Xianghan;Liu, Xiangtao;Zheng, Haixue;Zheng, Haixue

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关键词： African swine fever virus; autophagy; MGF-110-9L; PIK3C2B; TBK1

期刊名称：FASEB JOURNAL （ 影响因子：4.8； 五年影响因子：5.2 ）

ISSN： 0892-6638

年卷期： 2023 年 37 卷 6 期

页码：

收录情况： SCI

摘要： African swine fever (ASF) caused by African swine fever virus (ASFV) is a devastating disease for the global pig industry and economic benefit. The limited knowledge on the pathogenesis and infection mechanisms of ASF restricts progress toward vaccine development and ASF control. Previously, we illustrated that deletion of the MGF-110-9L gene from highly virulent ASFV CN/GS/2018 strains (ASFV?9L) results in attenuated virulence in swine, but the underlying mechanism remains unclear. In this study, we found that the difference in virulence between wild -type ASFV (wt- ASFV) and ASFV?9L strains was mainly caused by the difference in TANK Binding Kinase 1 (TBK1) reduction. TBK1 reduction was further identified to be mediated by the autophagy pathway and this degradative process requires the up-regulation of a positive autophagy regulation molecule- Phosphatidylinositol- 4-Phosphate 3-Kinase Catalytic Subunit Type 2 Beta (PIK3C2B). Moreover, TBK1 over-expression was confirmed to inhibit ASFV replication in vitro. In summary, these results indicate that wt-ASFV counteracts type I interferon (IFN) production by degrading TBK1, while ASFV?9L enhanced type I IFN production by weakening TBK1 reduction, clarifying the mechanism that ASFV?9L present the attenuated virulence in vitro.

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