African Swine Fever Virus E184L Protein Interacts with Innate Immune Adaptor STING to Block IFN Production for Viral Replication and Pathogenesis

文献类型： 外文期刊

第一作者： Zhu, Zixiang

作者： Zhu, Zixiang;Li, Shasha;Ma, Caina;Yang, Fan;Cao, Weijun;Liu, Huanan;Chen, Xia;Feng, Tao;Shi, Zhengwang;Tian, Hong;Zhang, Keshan;Liu, Xiangtao;Zheng, Haixue;Li, Shasha;Chen, Hongjun;Zheng, Haixue;Zheng, Haixue

作者机构：

期刊名称：JOURNAL OF IMMUNOLOGY （ 影响因子：4.4； 五年影响因子：5.2 ）

ISSN： 0022-1767

年卷期： 2023 年 210 卷 4 期

页码：

收录情况： SCI

摘要： African swine fever is one of the most serious viral diseases that affects domestic and wild pigs. The causative agent, African swine fever virus (ASFV), has evolved sophisticated immune evasion mechanisms that target both innate and adaptive immune responses. However, the underlying molecular mechanisms have not been fully understood. Here, we report that ASFV E184L protein inhibits host innate immune response via targeting the stimulator of IFN genes (STING)-mediated signaling pathway in both human embryonic kidney HEK-293T cells and porcine pulmonary alveolar macrophages. E184L interacts with STING, impairing dimerization and oligomerization of STING but not affecting its puncta formation at the perinuclear region. Furthermore, E184L disrupts STING-TBK1-IRF3 complex formation, leading to inhibition of STING phosphorylation, and IRF3 dimerization and nuclear translocation. The 1-20 aa region in E184L is essential for E184L-STING interaction and blocking IL-1b and type I IFN production. Deletion of E184L in ASFV considerably impairs antagonistic function of the virus in suppression of the STING -mediated antiviral response, an effect that is reversible by introduction of E184L. Importantly, the virulence of mutant ASFV lacking E184L is reduced in pigs compared with its parental virus due to induction of higher IFN production in vivo. Our findings indicate that ASFV E184L is an important antagonist of IFN signaling to evade host innate immune antiviral responses, which improves our understanding of immune evasion mechanisms of ASFV. The Journal of Immunology, 2023,210: 442-458.

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