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Related Experiment Videos

Simian virus 40 and human cancer

L Mutti1, M Carbone, G G Giordano

  • 1S. Maugeri Foundation, IRCCS, Rehabilitation Institute of Veruno/Varallo S., Italy.

Monaldi Archives for Chest Disease = Archivio Monaldi Per Le Malattie Del Torace
|August 5, 1998
PubMed
Summary

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.

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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.

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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.