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Selective killing of transformed rat cells by minute virus of mice does not require infectious virus production
E Guetta1, M Mincberg, S Mousset
1Biology Department, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Abstract:
Fischer rat fibroblasts, naturally resistant to killing by the fibrotropic strain of minute virus of mice [(parvovirus MVM(p)], became sensitive to MVM when transformed by polyomavirus. This sensitization did not involve an increase in the percentage of cells which synthesized viral capsid antigens or in the percentage of cells which produced infectious virus. The addition of anti-MVM antiserum to the growth medium of MVM-infected cells had only a small effect on their survival rates, indicating that the majority of the killing effect of MVM occurs in a single cycle of infection. The data indicate that cell killing by MVM is independent of infectious virus production and thus support the notion that the preferential cytolytic effect is affected by viral cytotoxic gene products which accumulate to intolerable levels in transformed cells but not in normal ones. Finally, using cells transformed with polyomavirus and genomic and subgenomic clones of polyomavirus, we showed that the extent of sensitization to killing by MVM depended on the transforming agent used.
Insights
Polyomavirus transformation sensitizes Fischer rat fibroblasts to minute virus of mice (MVM) killing. This enhanced cell death by MVM is independent of infectious virus production, suggesting a role for viral cytotoxic gene products.
Area of Science:
- Virology
- Cell Biology
- Oncogenic Viruses
Background:
- Fischer rat fibroblasts exhibit natural resistance to minute virus of mice (MVM).
- Polyomavirus transformation is known to alter cellular properties.
- Understanding virus-induced cell death mechanisms is crucial in virology.
Purpose of the Study:
- To investigate the effect of polyomavirus transformation on MVM-induced cell killing in Fischer rat fibroblasts.
- To determine if sensitization to MVM correlates with increased viral replication or antigen production.
- To elucidate the mechanism underlying MVM-mediated cytolysis in transformed cells.
Main Methods:
- Fibroblast cell culture and transformation using polyomavirus.
- Infection of normal and transformed cells with MVM (parvovirus MVM(p)).
- Analysis of viral capsid antigen synthesis, infectious virus production, and cell survival rates.
- Use of genomic and subgenomic polyomavirus clones.
Main Results:
- Polyomavirus-transformed fibroblasts became sensitive to MVM-induced killing.
- Sensitization did not correlate with increased MVM capsid antigen expression or infectious virus yield.
- MVM-mediated cell killing occurred predominantly within a single infectious cycle.
- The degree of MVM sensitization varied depending on the specific polyomavirus transforming agent used.
Conclusions:
- Cell killing by MVM is independent of infectious virus production.
- Viral cytotoxic gene products accumulating to high levels in transformed cells likely mediate MVM-induced cytolysis.
- The transforming agent influences the extent of sensitization to MVM-mediated cell death.