DNA损伤修复酶OGG1/MTH1抑制剂对非洲猪瘟病毒复制的影响

Effects of inhibitors of DNA repair enzymes OGG1 and MTH1 on the replication of African swine fever virus

摘要:

非洲猪瘟(African swine fever, ASF)是由非洲猪瘟病毒(African swine fever virus, ASFV)引起的一种动物疫病。2018年传入我国后迅速波及国内多个省份，给我国养猪业带来了巨大的冲击。由于对ASFV致病机制了解有限，导致ASF疫苗及抗病毒药物的研发遇到了极大挑战。本课题组前期研究发现，ASFV感染能引起宿主细胞内的氧化损伤应答，并且DNA氧化损伤修复酶在ASFV的感染中发挥重要作用，因此本研究采用RNA干扰、RT-qPCR、Western blotting、红细胞吸附(hemadsorption, HAD)、流式细胞技术等生物学方法，验证8-羟基鸟嘌呤DNA糖苷酶1 (8-oxoguanine DNA glycosylase 1, OGG1)/8-羟基鸟嘌呤核苷酸酶1 (8-oxoguanine nucleoside triphos-phatase, MTH1)小分子抑制剂对ASFV复制的影响，以评估靶向DNA氧化损伤修复酶的抗ASFV感染效果。本研究为抗非洲猪瘟药物的研发提供了借鉴及参考。

关键词:非洲猪瘟;抗病毒药物;碱基切除修复;8-羟基鸟嘌呤DNA糖苷酶1 (OGG1);8-羟基鸟嘌呤核苷酸酶1 (MTH1)

Abstract:

African swine fever virus (ASFV), as a contagious viral pathogen, is responsible for the occurrence of African swine fever (ASF), a rapidly spreading and highly lethal disease. Since ASFV was introduced into China in 2018, it has been quickly spread to many provinces, which brought great challenges to the pig industry in China. Due to the limited knowledge about the pathogenesis of ASFV, neither vaccines nor antiviral drugs are available. We have found that ASFV infection can induce oxidative stress responses in cells, and DNA repair enzymes play a key role in this process. This study employed RNA interference, RT-qPCR, Western blotting, Hemadsorption (HAD), and flow cytometry to investigate the effects of the inhibitors of DNA repair enzymes OGG1 and MTH1 on ASFV replication and evaluated the anti-ASFV effects of the inhibitors. This study provides reference for the development of anti-viral drugs.

Key words:African swine fever;antiviral drugs;base excision repair;8-oxoguanine DNA glycosylase 1 (OGG1);8-oxoguanine nucleoside triphos-phatase (MTH1)