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Simian virus 40 and human cancer
L Mutti1, M Carbone, G G Giordano
1S. Maugeri Foundation, IRCCS, Rehabilitation Institute of Veruno/Varallo S., Italy.
Abstract:
Deoxyribonucleic acid (DNA) oncoviruses can induce neoplastic transformation by interfering with proliferative proteins. Simian virus 40 (SV40) has been shown to induce brain tumors, osteosarcoma, lymphoid tumors and malignant mesothelioma in hamsters and SV40-like DNA sequences corresponding to the Rb-pocket binding domain of SV40 T-antigen (Tag) have been detected in the same human tumors. Since only a small percentage of people exposed to asbestos fibers develop a malignant mesothelioma, SV40 has been suspected to co-operate with the fibers in the neoplastic transformation or even to itself induce the onset of malignant mesothelioma in patients without expositive history. The mechanism that seems to be involved in the SV40-induced carcinogenesis process is mediated by interaction of Tag, both with p53 and Rb proteins, leading to their functional inactivation that is responsible for the removal of their inhibitory cell cycle effect which determines the increase of the number of cells entering the G1-S phase. Up to now the source of SV40 human infections has not yet been completely identified even though administration from 1957-1965 of SV40 contaminated polio vaccines is highly suspected. Horizontal infection by sexual transmission has been also hypothesized. Due to the important public health implications further investigations are required in order to establish both the source and the carcinogenetic role of simian virus 40 in humans.
Insights
Simian virus 40 (SV40) DNA oncoviruses may cause cancer by disrupting cell growth. SV40 T-antigen (Tag) inactivation of p53 and Rb proteins promotes cell cycle progression, potentially contributing to human tumors like mesothelioma.
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- Deoxyribonucleic acid (DNA) oncoviruses are known to induce neoplastic transformation by interfering with cellular proliferation.
- Simian virus 40 (SV40) has demonstrated oncogenic potential in hamsters, inducing various tumors including brain tumors, osteosarcoma, lymphoid tumors, and malignant mesothelioma.
- SV40-like DNA sequences, specifically the Rb-pocket binding domain of SV40 T-antigen (Tag), have been identified in human tumors, suggesting a potential role in human carcinogenesis.
Purpose of the Study:
- To investigate the suspected co-operation between SV40 and asbestos in the development of malignant mesothelioma.
- To explore the hypothesis that SV40 itself may induce malignant mesothelioma in individuals without asbestos exposure history.
- To elucidate the mechanism of SV40-induced carcinogenesis, focusing on the interaction of Tag with key tumor suppressor proteins.
Main Methods:
- Detection of SV40-like DNA sequences in human tumors.
- Analysis of the interaction between SV40 T-antigen (Tag) and cellular proteins p53 and Rb.
- Assessment of the impact of Tag-protein interaction on cell cycle regulation (G1-S phase transition).
Main Results:
- SV40 T-antigen (Tag) interaction with p53 and Rb proteins leads to their functional inactivation.
- This inactivation removes the inhibitory effect of p53 and Rb on the cell cycle.
- The functional inactivation results in an increased number of cells progressing from the G1 to the S phase of the cell cycle.
Conclusions:
- SV40 plays a significant role in the neoplastic transformation process by disrupting cell cycle control mechanisms.
- The administration of SV40-contaminated polio vaccines between 1957-1965 is a suspected source of human SV40 infections.
- Further research is crucial to identify the definitive source of SV40 human infections and confirm its carcinogenic role in human diseases, particularly malignant mesothelioma.