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 glycosylase 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 β (IFN-β) production during ASFV
infection and IFN-β 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-β 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.