Transformation by viruses: simian virus 40 as a model system.

Simian virus 40 (SV40), a DNA-containing tumor virus in the papovavirus group, represents an ideal model system for the analysis of the mechanism of viral-induced tumorigenesis because of the small size of its genome and its broad range of oncogenic potential. Viral genes persist and are expressed in SV40-transformed cells. Temperature-sensitive (ts) mutants of the virus have proved to be valuable tools for the identification and analysis of viral gene expression in transformed cells. Through the use of such mutants, it has been determined that a specific gene product (A-protein) is required to initiate cellular transformation. The role of virus genes in the maintenance of the transformed state was determined by transformation of the cells of mouse, hamster, and human origin by ts virus containing A-gene mutations. These cells were then examined under permissive and nonpermissive conditions for the presence of a variety of intracellular and surface alterations commonly associated with neoplastic transformation. From the results of such experiments, it has been concluded that an SV40-specific function is also necessary for the maintenance of at least some of the phenotypic properties of the transformed state. Indirect evidence, derived from a comparison of the biological and biochemical properties of the SV40-induced tumor (T) antigen and the gene A-protein, supports the idea that T-antigen is a product of the A-gene. One model devised to explain the mechanism by which the gene A-protein might function as an effector of transformation is presented.