Transcriptional activation of JC virus by human T-lymphotropic virus type I tax protein in human neuronal cell lines

Polyomavirus JC (JCV) causes the human demyelinating disease, progressive m ultifocal leukoencephalopathy (PML). The recent demonstration of cases of P ML in association with human T-lymphotropic virus type I (HTLV-I) infection prompted us to examine whether the HTLV-I-encoded regulatory protein Tax a ctivates JCV transcription. By employing a dual luciferase assay, we initia lly found that the expression of Tax activated the transcriptional potentia l of both early and late promoters of JCV in human neuronal but not in non- neuronal cells. We subsequently analyzed the mechanism of Tax-induced activ ation of the JCV promoter in neuronal cells with the following results: 1) the JCV promoter that lacks the NF-kappa B-binding motif could not be activ ated by Tax; 2) the overexpression of I kappa B alpha abolished Tax-induced transcriptional activation of the JCV promoter; 3) a Tax mutant M22) lacki ng the potential for activation via the NF-kappa B pathway did not activate the JCV promoter. Furthermore, Tax enhances the gene expression of JCV T a ntigen and VP1. We examined mechanisms of the cell-specific activation of t he JCV promoter by Tax. Electrophoretic mobility shift assay demonstrated t he presence of Tax-bound protein(s) that were specifically present in non-n euronal cells. This study is the first demonstration of the activation of J CV promoter by HTLV-I Tax in an NF-kappa B-dependent manner.