African swine fever virus (ASFV) infection induces oxidative stress and produces oxidative DNA damage bases, leading to oxidative DNA base damage, including the formation of 8-oxoguanine (8-oxoG). Prompt repair of these lesions is essential to maintain genome stability. The enzyme 8-oxoguanine DNA glycosylase 1 (OGG1) initiates the base excision repair (BER) pathway by recognizing and incising 8-oxoG, while also regulating multiple biological processes through interactions with host and viral proteins. In this study, we identified a specific interaction between the N-terminal region of ASFV DEAD-box helicase D1133L and OGG1, establishing a unique role for ASFV D1133L in DNA BER. Furthermore, we demonstrated for the first time that ASFV D1133L is a substrate for the histone acetyltransferases CBP/p300 in the nucleus. Conversely, deacetylation of D1133L by HDAC5, which predominantly occurs in the cytoplasm through its interaction with OGG1, markedly enhances OGG1 incision activity on 8-oxoG. Taken together, our findings reveal a previously unrecognized function of ASFV D1133L in promoting 8-oxoG repair by binding to OGG1 to safeguard genome integrity.
