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Caffeine restricts hepatitis B virus transcription by inhibiting <i>γ</i>-H2AX formation.

ABSTRACT: 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.

SUBMITTER: Liao F 

PROVIDER: S-EPMC12640983 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature

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Caffeine restricts hepatitis B virus transcription by inhibiting &lt;i&gt;γ&lt;/i&gt;-H2AX formation.

Liao Fangli F   Sun Siyi S   Huang Wenjuan W   Yang Liping L   Hu Qin Q   Chen Weixian W   Tu Chaolin C   Jiang Linshan L  

Frontiers in microbiology 20251110

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 <i>γ</i>-H2AX, which in turn diminishes HBV transcription. Functional assays revealed that <i>γ</i>-H2AX enhances HBV core promoter activity by facilitating the recruitment of peroxisome proliferator-activated  ...[more]