T antigen of human papovavirus JC stimulates transcription of the POU domain factor Tst-1/Oct6/SCIP.

Human papovavirus JC exhibits a strong tropism for glial cells in vivo. To a large extent, this effect is due to the pronounced glia specificity of viral gene expression, which is mediated by the specific interaction of glial transcription factors such as Tst-1/Oct6/SCIP with viral promoter sequences. Here we show that, in return, expression of the glial transcription factor Tst-1/Oct6/SCIP can be strongly activated by T antigen, the early gene product of JC virus, in a dose-dependent manner. In transient transfection experiments, stimulation by T antigen was entirely dependent on a 335-bp segment of the Tst-1/Oct6/SCIP gene promoter that included the transcriptional start site. The same fragment was also bound by purified T antigen in immunoprecipitation assays due to the presence of three closely spaced and tandemly oriented GAGGC pentamers. However, when this array of pentamers was mutated so that binding of T antigen was strongly reduced, T-antigen-dependent transcriptional activation remained unaffected. Thus, similar to viral late gene expression, transcriptional stimulation of the Tst-1/Oct6/SCIP gene by T antigen was not dependent on binding to GAGGC pentamers present within the promoter. Nevertheless, our data provide strong support for a model in which JC virus influences gene expression of its host cell via its early gene product in a manner favourable for its own propagation.