刺
生物
泛素
病毒学
坦克结合激酶1
病毒
信号转导
基因
丝裂原活化蛋白激酶激酶
遗传学
细胞生物学
工程类
航空航天工程
蛋白激酶C
作者
Li Huang,Wenjie Xu,Hongyang Liu,Mengdi Xue,Xiaohong Liu,Kunli Zhang,Liang Hu,Jiangnan Li,Xuemin Liu,Zhida Xiang,Jun Zheng,Changyao Li,Weiye Chen,Zhigao Bu,Tao Xiong,Changjiang Weng
出处
期刊:Journal of Immunology
[American Association of Immunologists]
日期:2021-11-10
卷期号:207 (11): 2754-2769
被引量:77
标识
DOI:10.4049/jimmunol.2100320
摘要
Abstract 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-β 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 І 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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