OGG1 inhibition suppresses African swine fever virus replication

文献类型： 外文期刊

第一作者： Fan, Jie

作者： Fan, Jie;Geng, Shuxian;Zeng, Qiaoying;Fan, Jie;Lv, Xinqian;Yang, Saixia;Geng, Shuxian;Yang, Jifei;Zhao, Yaru;Zhang, Zhonghui;Liu, Zhijie;Guan, Guiquan;Luo, Jianxun;Yin, Hong;Niu, Qingli;Yin, Hong

作者机构：

关键词： African swine fever virus (ASFV); 8-oxoguanine DNA glycosylase 1 (OGG1); 8-oxo-7; 8-dihydroguanine (8-oxoG); Inhibitors; Antiviral effect

期刊名称：VIROLOGICA SINICA （ 影响因子：5.5； 五年影响因子：4.9 ）

ISSN： 1674-0769

年卷期： 2023 年 38 卷 1 期

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收录情况： SCI

摘要： African swine fever virus (ASFV) is an important pathogen that causes a highly contagious and lethal disease in swine, for which neither a vaccine nor treatment is available. The DNA repair enzyme 8-oxoguanine DNA gly-cosylase 1 (OGG1), which excises the oxidative base lesion 8-oxo-7,8-dihydroguanine (8-oxoG), has been linked to the pathogenesis of different diseases associated with viral infections. However, the role of OGG1-base excision repair (BER) in ASFV infection has been poorly investigated. Our study aimed to characterize the alteration of host reactive oxygen species (ROS) and OGG1 and to analyse the role of OGG1 in ASFV infection. We found that ASFV infection induced high levels and dynamic changes in ROS and 8-oxoG and consistently increased the expression of OGG1. Viral yield, transcription level, and protein synthesis were reduced in ASFV-infected primary alveolar macrophages (PAMs) treated by TH5487 or SU0268 inhibiting OGG1. The expression of BER pathway associated proteins of ASFV was also suppressed in OGG1-inhibited PAMs. Furthermore, OGG1 was found to negatively regulate interferon beta (IFN-beta) production during ASFV infection and IFN-beta could be activated by OGG1 inhibition with TH5487 and SU0268, which blocked OGG1 binding to 8-oxoG. Additionally, the interaction of OGG1 with viral MGF360-14-L protein could disturb IFN-beta production to further affect ASFV replication. These results suggest that OGG1 plays the crucial role in successful viral infection and OGG1 inhibitors SU0268 or TH5487 could be used as antiviral agents for ASFV infection.

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