Epstein-Barr virus (EBV) establishes lifelong latency in human cells and can periodically reactivate, contributing to several cancers. However, the molecular mechanisms that disrupt EBV latency, particularly those driven by oxidative stress, require further investigation. In this study, we provide evidence that oxidative DNA damage, particularly the formation of 8-oxoguanine and its repair enzyme OGG1, is involved in EBV reactivation. We demonstrated that OGG1 is recruited to EBV regulatory regions under oxidative stress conditions and is associated with the transcriptional activation of immediate-early and early lytic genes. Further experiments showed that pharmacological inhibition of OGG1 DNA binding significantly suppressed EBV lytic gene expression, supporting a functional role for OGG1 in viral reactivation. Mechanistically, our findings suggest that OGG1 may contribute to EBV lytic activation through a noncanonical mechanism independent of its glycosylase activity. These findings provide insight into how EBV may exploit host oxidative DNA damage responses to facilitate latency disruption and suggest that targeting OGG1 may offer a potential strategy to limit EBV reactivation and EBV-associated diseases.
Hao, W., Wang, X., Liu, G., Li, J., Ba, X., Pan, L., Boldogh, I., Duan, Z.
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