Viral exploitation of p300/CBP at the virus-cancer interface: Chromatin regulation, oncogenesis, immune evasion, and therapeutic targeting.

The transcriptional coactivators p300 and CREB-binding protein (CBP) integrate chromatin remodeling, enhancer activity, lysine acetylation, immune signaling, and tumor-suppressor control, making them recurrent targets of viral proteins. This narrative review examines p300/CBP at the virus-cancer interface, prioritizing HTLV-1, high-risk HPV, EBV, KSHV, HBV, and HCV. We distinguish physical interaction, biochemical modulation, functional reliance, and therapeutic confirmation and compare how viral factors recruit, inhibit, degrade, or redistribute these coactivators during persistence, immune evasion, and malignant progression. Evidence from non-oncogenic viruses is retained only when it clarifies conserved mechanisms or therapeutic liabilities. Preclinical studies support catalytic, interaction-selective, and virus-specific targeting strategies, but human evidence is limited to early-phase PRI-724/OP-724 antifibrotic studies in viral cirrhosis. Because p300/CBP also support normal transcription and antiviral immunity, systemic inhibition may cause substantial toxicity. Overall, p300/CBP are best viewed as context-dependent regulatory hubs, and translation will require paralog-, domain-, and disease-specific validation.