African Swine Fever Virus pI215L Negatively Regulates cGAS-STING Signaling Pathway through Recruiting RNF138 to Inhibit K63-Linked Ubiquitination of TBK1

文献类型： 外文期刊

第一作者： Huang, Li

作者： Huang, Li;Xu, Wenjie;Liu, Hongyang;Xue, Mengdi;Liu, Xiaohong;Zhang, Kunli;Hu, Liang;Li, Jiangnan;Liu, Xuemin;Xiang, Zhida;Zheng, Jun;Li, Changyao;Chen, Weiye;Bu, Zhigao;Weng, Changjiang;Xu, Wenjie;Xiang, Zhida;Xiong, Tao;Weng, Changjiang

作者机构：

期刊名称：JOURNAL OF IMMUNOLOGY （ 影响因子：5.426； 五年影响因子：6.178 ）

ISSN： 0022-1767

年卷期： 2021 年 207 卷 11 期

页码：

收录情况： SCI

摘要： African swine fever is a severe animal infectious disease caused by African swine fever virus (ASFV), and the morbidity and mortality associated with virulent ASFV isolates are as high as 100%. Previous studies showed that the ability of ASFV to antagonize IFN production is closely related to its pathogenicity. Here, we report that ASFV HLJ/18 infection induced low levels of type I IFN and inhibited cGMP-AMP-induced type I IFN production in porcine alveolar macrophages that were isolated from specific pathogen-free Landrace piglets. Subsequently, an unbiased screen was performed to screen the ASFV genes with inhibitory effects on the type I IFN production. ASFV pI215L, a viral E2 ubiquitin-conjugating enzyme, was identified as one of the strongest inhibitory effectors on the production of type I IFN. Knockdown of pI215L expression inhibited ASFV replication and enhanced IFN-beta production. However, inhibition of type I IFN production by pI215L was independent of its E2 enzyme activity. Furthermore, we found that pI215L inhibited type I IFN production and K63-linked polyubiquitination of TANK-binding kinase 1 through pI215L-binding RING finger protein 138 (RNF138). ASFV pI215L enhanced the interaction between RNF138 and RNF128 and promoted RNF138 to degrade RNF128, which resulted in reduced K63-linked polyubiquitination of TANK-binding kinase 1 and type I IFN production. Taken together, our findings reveal a novel immune escape mechanism of ASFV, which provides a clue to the design and development of an immune-sensitive attenuated live vaccine.

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