African swine fever virus pB318L, a trans-geranylgeranyl-diphosphate synthase, negatively regulates cGAS-STING and IFNAR-JAK-STAT signaling pathways

文献类型： 外文期刊

第一作者： Liu, Xiaohong

作者： Liu, Xiaohong;Chen, Hefeng;Ye, Guangqiang;Liu, Hongyang;Feng, Chunying;Chen, Weiye;Hu, Liang;Zhou, Qiongqiong;Zhang, Zhaoxia;Li, Jiangnan;Zhang, Xianfeng;He, Xijun;Guan, Yuntao;Wu, Zhengshuang;Zhao, Dongming;Bu, Zhigao;Weng, Changjiang;Huang, Li;Zhang, Zhaoxia;Li, Jiangnan;Weng, Changjiang;Huang, Li

作者机构：

期刊名称：PLOS PATHOGENS （ 影响因子：6.7； 五年影响因子：6.7 ）

ISSN： 1553-7366

年卷期： 2024 年 20 卷 4 期

页码：

收录情况： SCI

摘要： African swine fever (ASF) is an acute, hemorrhagic, and severe infectious disease caused by the ASF virus (ASFV). ASFV has evolved multiple strategies to escape host antiviral immune responses. Here, we reported that ASFV pB318L, a trans-geranylgeranyl-diphosphate synthase, reduced the expression of type I interferon (IFN-I) and IFN-stimulated genes (ISGs). Mechanically, pB318L not only interacted with STING to reduce the translocation of STING from the endoplasmic reticulum to the Golgi apparatus but also interacted with IFN receptors to reduce the interaction of IFNAR1/TYK2 and IFNAR2/JAK1. Of note, ASFV with interruption of B318L gene (ASFV-intB318L) infected PAMs produces more IFN-I and ISGs than that in PAMs infected with its parental ASFV HLJ/18 at the late stage of infection. Consistently, the pathogenicity of ASFV-intB318L is attenuated in piglets compared with its parental virus. Taken together, our data reveal that B318L gene may partially affect ASFV pathogenicity by reducing the production of IFN-I and ISGs. This study provides a clue to design antiviral agents or live attenuated vaccines to prevent and control ASF. African swine fever virus (ASFV) causes a highly lethal swine disease in many countries, severely affecting the pig industry. Until now, African swine fever has caused substantial economic losses to the world pig industry because of the lack of commercial vaccines and drugs. Therefore, there is an urgent need for efficient commercialized vaccines to prevent and control the disease. It has been reported that the ability of ASFV to escape host antiviral immune responses is closely related to its pathogenicity, and deletion of ASFV virulence-related gene(s) may contribute to the development of attenuated live vaccines. In this study, we found that pB318L reduces the production of IFN-I induced by cGAS-STING and ISGs induced by IFN-alpha. As a virulence-related gene, interruption of B318L significantly attenuated ASFV pathogenicity. Our findings provide a new clue to understand the functions of ASFV-encoded pB318L and its role in viral infection-induced pathogenesis, which might help design antiviral agents or live attenuated vaccines to control ASF.

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