Transformation of Rabbit Vascular Smooth Muscle Cells by SV40 Virus
Evidence is accumulating that viruses may participate in atherogenesis. In chickens, infection with Marek’s disease virus induces atherosclerotic lesions in the absence of hypercholesterolemia. In humans, several distinct viruses have been found in atherosclerotic lesions. To assess the possible effects of viral transformation on vascular smooth muscle cell growth and metabolism, we infected subconfluent cultured rabbit arterial smooth muscle cells with simian virus 40 (SV40), Baylor strain, wild type. Three weeks after infection, a transformed cell line was isolated. The transformed cells expressed intranuclear SV40 T antigen yet still retained smooth muscle characteristics as documented by a uniform positive reaction with antibodies against smooth muscle cell-specific actin. These transformed cells were further subcultured, and 18 clones were obtained, each exhibiting a characteristic phenotype. The morphological appearances of the cells in the different clones ranged from multinucleated giant cells of variable shape to small uniform-sized cells. The transformed cell clones contained significantly more polyploid cells than control cells, and the modal chromosome number ranged from 41 to 83, whereas the control smooth muscle cells maintained a modal diploid number of 44. The transformed cells grew both faster and to a higher saturation density than did control smooth muscle cells in culture medium containing either 1% or 5% fetal calf serum. When the cells were incubated in the presence of lipoprotein-deficient serum, the clones displayed greater diversity in their intracellular lipid content. In preliminary experiments, incubation of certain clonal cell lines with lipoproteins resulted in massive lipid overloading. These results indicate that virus-transformed smooth muscle cells exhibit phenotypic changes that should be of considerable value for studying the consequences of viral infection of vascular smooth muscle cells in atherogenesis.
KeywordsSmooth Muscle Cell Vascular Smooth Muscle Cell Multinucleated Giant Cell Clonal Cell Line SV40 Virus
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- Nachtigal, M., Greenspan, P., Terracio, L., Mayer, E. P., and Fowler, S. D., 1985, Transformation of rabbit vascular smooth muscle cells by SV40 virus, J. Cell Biol. 101:11 la.Google Scholar