INTERNATIONAL CONGRESS OF
CancerGenetics
Oncoviruses and Epigenetic Alterations: Double Drivers of Tumorigenesis
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Sheida Khajeh Talkhouncheh,1,*
1. Azad University of Najafabad , Isfahan , Iran
- Introduction: A subset of human cancers can be traced to persistent infections with specific oncoviruses that promote cellular transformation through synergistic genetic and epigenetic processes. Canonical mechanisms include direct integration of viral genomes (e.g., HPV, HBV) and expression of viral oncoproteins that subvert host cell control systems. However, evidence now reveals that oncoviruses induce profound reprogramming of the epigenome, which promotes oncogene activation, tumor suppressor gene silencing, chronic inflammation, and immune evasion. These epigenetic scars can persist even after the virus is cleared, increasing lifelong cancer risk.
- Methods: Recent advances in multi-omics, including genome-wide methylation, chromatin immunoprecipitation sequencing (ChIP-seq), and advanced 3D chromatin conformation capture, alongside in vitro and in vivo infection models, underpin much of our knowledge of virus-induced epigenetic alterations. Researchers frequently deploy bisulfite sequencing to analyze methylation, RNA-seq for transcriptomic shifts, and CRISPR/Cas9 to interrogate specific gene functions. Clinical cohorts, animal models, and engineered cell line systems support association and functional studies, helping clarify mechanisms in relevant tissues.
- Results: Epigenetic reprogramming is a common feature across diverse oncovirus families. For example, HPV’s E6 and E7 proteins recruit DNA methyltransferases to silence host tumor suppressors and modulate histone methylation, supporting immune escape, malignant transformation, and maintenance of stemness features in epithelial cells. EBV and KSHV encode viral proteins that interact with host chromatin modifiers (e.g., LMP1, EBNA1, LANA), leading to altered host DNA methylation and histone marks, silencing of key apoptosis regulators, and persistent latent infection in lymphoepithelial tissues. HBV and HCV infections reshape the hepatic epigenome, leading to promoter hypermethylation of tumor suppressors and global deregulation of chromatin accessibility, which is often detectable long after viral antigens are cleared. These effects are complemented by the disruption of non-coding RNAs, including microRNAs and long non-coding RNAs, which further modulate chromatin and transcriptional landscapes. In haematological and solid tumors, persistent viral infections often result in cumulative mutations and widespread hypo- or hypermethylation, tipping the functional balance toward uncontrolled proliferation, apoptosis evasion, and increased metastatic potential. Comparative analysis shows that viral-driven tumors are often distinguishable from their non-virus-associated counterparts by unique epigenetic and transcriptional signatures, exemplified by EBV-positive lymphomas and HPV-driven cervical or head and neck cancers.
- Conclusion: Oncoviruses serve as dual drivers of tumorigenesis: not only do they introduce foreign oncogenes or perpetuate chronic inflammation, but they also orchestrate heritable and persistent disruptions to host epigenetic regulatory networks. This dual action accelerates cancer initiation, progression, and resistance to therapy. Targeting the epigenetic machinery altered by oncoviruses—through the use of epigenetic drugs, tailored immunotherapies, and possibly gene-editing technologies—offers promising strategies to reverse viral oncogenic scars and improve patient outcomes. Future research must continue to dissect virus-specific epigenetic landscapes and develop integrated therapeutic approaches for virus-driven cancers.
- Keywords: Oncovirus_Epigenetics_DNAmethylation_Chromatin remodeling_Tumorigenesis
