When introduced into the germ line of mice, the simian virus 40 (SV40)
T antigen under the control of its own transcriptional enhancer and promoter selectively induced
tumors in the choroid plexus as well as
thymic hyperplasia and kidney pathology. In contrast, the JC virus (JCV)
T antigen under the control of its own regulatory sequences induced hypomyelination of the central nervous system and
tumors of neural origin. Since SV40 and JCV have extensive sequence homology, except for their transcriptional control regions, these observations suggest but do not prove that, although the diseases induced by the two viruses, are consequences of the transforming gene, they are determined predominantly by the respective viral enhancers and promoters. To test this hypothesis, the regulatory regions of the two viruses were exchanged, and transgenic mice were derived with either chimeric construct. Like wild-type JCV, the construct containing the SV40
T antigen under the control of the JCV regulatory region induced hypomyelination of the central nervous system and neural
tumors. Surprisingly, mice with this construct also developed choroid plexus
carcinomas. Like the wild-type SV40 transgenic mice, mice with the JCV
T antigen under the control of the SV40 enhancer and promoter developed
choroid plexus tumors and renal pathology. Unexpectedly, they also had
hyperplasia of the thyroid follicular cells. These findings not only provide direct evidence for the specificity of the respective viral regulatory region but also, more importantly, show that the transforming genes play a critical role in determining viral pathogenesis.