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Published on: September 12, 2019
Human mesothelial cells are unusually susceptible to simian virus 40-mediated transformation and asbestos
M Bocchetta1, I Di Resta, A Powers
1Cancer Immunology Program, Department of Pathology, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL 60153, USA.
Abstract:
Mesothelioma, a malignancy associated with asbestos, has been recently linked to simian virus 40 (SV40). We found that infection of human mesothelial cells by SV40 is very different from the semipermissive infection thought to be characteristic of human cells. Mesothelial cells are uniformly infected but not lysed by SV40, a mechanism related to p53, and undergo cell transformation at an extremely high rate. Exposure of mesothelial cells to asbestos complemented SV40 mutants in transformation. Our data provide a mechanistic explanation for the ability of SV40 to transform mesothelial cells preferentially and indicate that asbestos and SV40 may be cocarcinogens.
Insights
Simian virus 40 (SV40) uniformly infects human mesothelial cells, promoting high-rate cell transformation. Asbestos exposure complements SV40 mutants, suggesting they are cocarcinogens in mesothelioma development.
Area of Science:
- Oncology
- Virology
- Cell Biology
Background:
- Mesothelioma is a malignancy linked to asbestos exposure.
- Simian virus 40 (SV40) has been recently associated with mesothelioma.
- The interaction between SV40 and human mesothelial cells is not fully understood.
Purpose of the Study:
- To investigate the infection mechanism of SV40 in human mesothelial cells.
- To explore the role of asbestos in SV40-mediated mesothelial cell transformation.
- To elucidate the potential cocarcinogenic role of SV40 and asbestos in mesothelioma.
Main Methods:
- Infection of human mesothelial cells with SV40.
- Analysis of cell lysis and transformation rates.
- Assessment of SV40 mutant complementation by asbestos exposure.
Main Results:
- SV40 uniformly infects human mesothelial cells without lysis.
- Mesothelial cells undergo high-rate transformation following SV40 infection, involving p53.
- Asbestos exposure complements SV40 mutants, enhancing transformation.
Conclusions:
- SV40 preferentially transforms mesothelial cells through a unique infection mechanism.
- Asbestos and SV40 act as cocarcinogens, contributing to mesothelioma development.
- These findings offer a mechanistic explanation for SV40's role in asbestos-related cancers.
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