Aflatoxin B1 induces subtle but coordinated histone modifications in Epstein-Barr virus infected and non-infected Burkitt lymphoma cells.

Aflatoxin B1 (AFB1), a potent dietary carcinogen, and Epstein-Barr virus (EBV), an oncogenic virus, are both implicated in cancer development, particularly in endemic regions. However, the combined effects of AFB1 exposure and EBV infection on the epigenetic landscape remain poorly understood. This study investigates the impact of AFB1 and EBV on histone post-translational modifications (hPTMs) in Burkitt lymphoma (BL) cells through an integrative approach combining untargeted mass spectrometry-based profiling and a time-lapse experimental design. Our results reveal subtle, yet reproducible and dynamic alterations in histone methylation and acetylation patterns over time in all cells. Specifically, AFB1 exposure induced an increase in H3K27me3 levels, which in the case of EBV infected cells, counteracts the decrease observed at baseline compared to uninfected cells. Additionally, changes in acetylation patterns of H4 N-tail residues and key regulatory proteins suggest potential disruptions in chromatin accessibility and transcriptional regulation. Our correlation and network-based analyses further highlight coordinated epigenetic shifts in response to AFB1, with key acetylation hubs emerging within the histone PTM profile. Despite subtle differences, no significant divergence in overall hPTM responses was detected between EBV-infected and uninfected cells, emphasizing the subtlety of the EBV effect on AFB1 exposure. Future research should explore locus-specific epigenetic changes and therapeutic interventions targeting hPTMs to mitigate cancer risk associated with AFB1 exposure and EBV infection.