The cytotoxicity of the autonomous parvovirus minute virus of mice nonstructural proteins in FR3T3 rat cells depends on oncogene expression.
AUTOR(ES)
Mousset, S
RESUMO
The nonstructural (NS) proteins of the autonomous parvovirus minute virus of mice are involved in viral DNA replication and in the regulation of homologous and heterologous promoters. Moreover, NS products have proved to be cytotoxic, especially for transformed cells. We show here that intracellular accumulation of NS products is not sufficient to kill rat fibroblasts from the established cell line FR3T3, which is phenotypically normal in several respects. FRNS cell lines were obtained by stable transfection of FR3T3 cells by a vector carrying the NS genes under the control of the hormone-inducible long terminal repeat promoter of the mouse mammary tumor virus. In the presence of dexamethasone, the NS proteins were synthesized without associated cell death. Transformation of FRNS cells with the c-Ha-ras oncogene or polyomavirus oncogenes had little effect on their capacity for NS induction, as measured at both concentration and transactivating activity levels, yet the transformants were now dying within a few days in the presence of the inducer. The same results were obtained with cells stably transfected by a vector expressing the NS1 product alone, suggesting that in this system there is no cooperation between NS1 and NS2 for maximal cytopathic effect. Cell mortality after NS protein induction was quantitatively related to the yield of oncogene expression, while NS-1 was not limiting in this respect. Our results show that the NS1 protein is not lethal unless cellular factors that may depend on oncogene expression trigger its cytotoxicity.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=237064Documentos Relacionados
- Organization of nonstructural genes of the autonomous parvovirus minute virus of mice.
- The cytotoxicity of the parvovirus minute virus of mice nonstructural protein NS1 is related to changes in the synthesis and phosphorylation of cell proteins.
- The complete DNA sequence of minute virus of mice, an autonomous parvovirus.
- Sensitization of transformed rat fibroblasts to killing by parvovirus minute virus of mice correlates with an increase in viral gene expression.
- Construction of an infectious molecular clone of the autonomous parvovirus minute virus of mice.