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How can integration of viral DNA contribute to malignant transformation of cells?

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Diagram illustrating the process of retrovirus infection and reverse transcription, showing a retrovirus entering a host cell, releasing viral RNA, reverse transcriptase converting RNA to DNA, integration into the host genome, transcription of new viral RNA, assembly of new virions, and budding from the cell. — Reverse transcriptase After a retrovirus infects a cell, an enzyme known as reverse transcriptase converts viral RNA into proviral DNA in the cytoplasm. Proviral DNA then enters the nucleus, where it is incorporated into the host cell's DNA.

The integration of viral DNA into a host cell's genome can lead to malignant transformation through several mechanisms, often involving the activity of the reverse transcriptase enzyme in retroviruses.12

When retroviruses infect a cell, reverse transcriptase converts the viral RNA genome into double-stranded DNA, which is then integrated into the host cell's chromosomes. This process contributes to cancer in two primary ways:13

Insertional Mutagenesis: Slowly transforming retroviruses may integrate their genomes directly into or near critical sites in the host cell's DNA, such as proto-oncogenes. This can cause these genes to become overactive oncogenes, which instruct the cell to divide uncontrollably, or it may inactivate tumor suppressor genes.12
Viral Oncogenes: Acutely transforming retroviruses can incorporate host genetic material into their own genomes during previous infections. When this altered genetic material is integrated into a new host cell, it acts as a potent oncogene, driving rapid and abnormal cell proliferation.2

Ultimately, these changes disrupt the normal regulation of cell growth and apoptosis, leading to the uncontrolled growth characteristic of cancer.1