Caffeine restricts hepatitis B virus transcription by inhibiting γ-H2AX formation

This is the authors' abstract. We don't add key points for this paper.

The influence of caffeine on human health has been widely studied, but its relevance to hepatitis B virus (HBV) remains unclear. Here, we report that exogenous caffeine suppresses HBV RNA and core protein expression in hepatoma cells. Mechanistically, caffeine reduces the DNA damage marker γ -H2AX, which in turn diminishes HBV transcription. Functional assays revealed that γ -H2AX enhances HBV core promoter activity by facilitating the recruitment of peroxisome proliferator–activated receptor- α (PPARα). Chromatin immunoprecipitation confirmed that reduced γ -H2AX levels impair the binding of PPARα to the HBV core promoter. These findings establish a γ -H2AX–PPARα signaling axis that promotes HBV transcription and demonstrate that caffeine interferes with this pathway. In summary, our study demonstrated that γ -H2AX may serve as a nutritionally targetable node, supporting dietary and adjunct strategies for HBV management.