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Review
. 2025 Aug 19;99(8):e0056225.
doi: 10.1128/jvi.00562-25. Epub 2025 Jul 23.

Genome integration of human DNA oncoviruses

Affiliations
Review

Genome integration of human DNA oncoviruses

Zuzana Vojtechova et al. J Virol. .

Abstract

Tumors of infectious origin globally represent 13%. Oncogenic DNA viruses such as human papillomavirus (HPV), hepatitis B virus (HBV), and Epstein-Barr virus (EBV) are responsible for approximately 60% of these tumors. These oncoviruses are extensively studied to understand their role in cancer development, particularly through viral genome integration into the host DNA. Retroviruses require integration mediated by viral integrase for persistence, whereas DNA oncoviruses do not need integration for replication; instead, integration occurs incidentally. This process often targets fragile sites in the human genome, causing structural rearrangements that disrupt genes, activate proto-oncogenes, and increase genomic instability, all contributing to tumorigenesis. Integration near promoter regions and active genes is closely linked to carcinogenesis, highlighting its importance in developing diagnostic and therapeutic strategies. This review summarizes viral integration's role in oncogenesis, mechanisms of integration, and methods to study this process, focusing on DNA tumor viruses such as HBV, EBV, HPV, and Merkel cell polyomavirus.

Keywords: Epstein-Barr virus; hepatitis B virus; human papillomavirus; integration; virus.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig 1
Fig 1
Diagram illustrating the main mechanisms of viral integration and the host genome regions that can be affected by viral integration, resulting in changes in gene expression. Created with BioRender.com.
Fig 2
Fig 2
Patterns of MCPyV integration. (A) Linear integration pattern (L—left integration breakpoint and R—right integration breakpoint) and (B) Z-pattern integration. (Adapted from reference .)
Fig 3
Fig 3
Comparison of the characteristics of particular DNA tumor viruses. Created with BioRender.com.

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