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Antiviral activity of tumor-suppressor pathways: clues from molecular piracy by KSHV
1Department of Pathology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. psm9@columbia.edu
Abstract:
A common feature of many tumor viruses is that they possess genes that produce specific proteins to inhibit major cellular tumor-suppressor pathways. Despite intensive studies, the reasons why these diverse and unrelated viruses have independently evolved oncogenes remains obscure. Kaposi-sarcoma-associated herpesvirus (KSHV or HHV8) has pirated a number of recognizable cellular genes that are key to cell survival and proliferation. In this review, we provide an overview of the known activities of these viral genes and show that many of these pirated proteins affect the same cellular pathways targeted by other, unrelated tumor viruses. We speculate that tumor-suppressor pathways are used by the cell as a primary defense against persistent virus infection, in addition to their well-known activity in regulating cell proliferation.
Insights
Many tumor viruses use oncogenes to inhibit cellular tumor-suppressor pathways. Kaposi-sarcoma-associated herpesvirus (KSHV) also hijacks cellular genes, suggesting these pathways are a key defense against viral infections.
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- Tumor viruses often encode oncogenes that disrupt cellular tumor-suppressor pathways.
- The evolutionary reasons for independent oncogene acquisition by diverse viruses remain unclear.
- Kaposi-sarcoma-associated herpesvirus (KSHV, or HHV8) is known to acquire cellular genes crucial for cell survival and proliferation.
Purpose of the Study:
- To review the functions of KSHV-pirated genes.
- To compare the cellular pathways targeted by KSHV with those targeted by other tumor viruses.
- To explore the role of tumor-suppressor pathways in antiviral defense.
Main Methods:
- Literature review of KSHV oncogenes and their cellular targets.
- Comparative analysis of viral oncogene activities across different virus families.
- Synthesis of current knowledge on viral hijacking of tumor-suppressor pathways.
Main Results:
- KSHV pirated cellular genes encode proteins with diverse functions.
- Many KSHV-encoded proteins target the same cellular pathways as oncogenes from unrelated tumor viruses.
- These shared targets include key regulators of cell survival and proliferation.
Conclusions:
- The convergent evolution of oncogenes targeting similar cellular pathways suggests a conserved viral strategy.
- Tumor-suppressor pathways may serve a dual role: regulating cell proliferation and acting as a primary defense against persistent viral infections.
- Understanding these viral-cellular interactions is crucial for developing novel antiviral and anticancer therapies.