Epigenetic Dysregulation in Virus-Associated Neoplasms

Area of Science:

• Epigenetics
• Virology
• Oncology

Background:

• Human tumor viruses interact with host epigenetic machinery.
• These interactions reprogram cellular gene expression patterns.
• Altered DNA methylation and histone modifications are hallmarks of virus-associated cancers.

Purpose of the Study:

• To review the impact of viral oncoproteins on host cell epigenomes.
• To highlight alterations in DNA methylation and histone modification by various human tumor viruses.
• To discuss the consequences of these epigenetic changes on host gene expression and tumorigenesis.

Main Methods:

• Review of existing literature on viral oncoproteins and epigenetic machinery.
• Analysis of studies reporting changes in DNA methylation and histone modification in virus-associated neoplasms and cell lines.
• Examination of specific examples including KSHV, HBV, HCV, HPV, MCPyV, EBV, adenovirus, and HTLV-I.

Main Results:

• Viral oncoproteins alter DNA methyltransferases and the cellular methylome.
• Methylation-mediated silencing of cellular promoters is observed in multiple virus-associated cancers.
• Promoter activation via DNA hypomethylation or histone modification induction by viral oncoproteins also occurs.
• Hepatitis C virus (HCV) infection induces large, hypomethylated chromatin blocks.
• Hepatitis B virus (HBV) oncoprotein HBx downregulates DNMT3B, leading to demethylation.
• Human T-cell lymphotropic virus type I (HTLV-I) oncoproteins Tax and HBZ modulate histone modifications.

Conclusions:

• Viral oncoproteins are key players in epigenetic reprogramming of host cells.
• These epigenetic alterations contribute to the development and progression of virus-associated cancers.
• Targeting viral-induced epigenetic changes presents potential therapeutic strategies.