How virus persistence can initiate the tumorigenesis process

Area of Science:

• Oncology
• Virology
• Molecular Biology

Background:

• Human oncogenic viruses are considered necessary but not sufficient for cancer initiation.
• Existing models fail to explain the rarity and long latency of virus-associated tumor development.

Purpose of the Study:

• To propose a general mechanism for viral oncogenesis, considering both RNA and DNA viruses.
• To suggest viruses can be both necessary and sufficient for initiating human tumorigenesis.

Main Methods:

• Review of emerging evidence on viral induction of DNA damage.
• Analysis of viral subversion of DNA damage response pathways.
• Examination of virus-induced epigenetic disturbances.

Main Results:

• Viruses can induce DNA damage and disrupt cellular repair mechanisms.
• A "hit and rest" model is proposed, where initial viral damage creates a reservoir of cells prone to further mutations.
• Viral persistence and reactivation contribute to cumulative genetic and epigenetic damage.

Conclusions:

• Viruses, through a "hit and rest" mechanism, can be sufficient in initiating tumorigenesis.
• This model reconciles the mutagenic potential of viruses with the rare occurrence of cancer in infected individuals.
• Tumorigenesis results from rare cumulative damage from viral infections, latency, and reactivations.