title: Transcriptional activation of JC virus by human T-lymphotropic virus type I Tax protein in human neuronal cell lines.
abstract: Polyomavirus JC (JCV) causes the human demyelinating disease, progressive multifocal leukoencephalopathy (PML). The recent demonstration of cases of PML in association with human T-lymphotropic virus type I (HTLV-I) infection prompted us to examine whether the HTLV-I-encoded regulatory protein Tax activates JCV transcription. By employing a dual luciferase assay, we initially found that the expression of Tax activated the transcriptional potential 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 activation of the JCV promoter in neuronal cells with the following results: 1) the JCV promoter that lacks the NF-kappaB-binding motif could not be activated by Tax; 2) the overexpression of IkappaBalpha abolished Tax-induced transcriptional activation of the JCV promoter; 3) a Tax mutant (M22) lacking the potential for activation via the NF-kappaB pathway did not activate the JCV promoter. Furthermore, Tax enhances the gene expression of JCV T antigen and VP1. We examined mechanisms of the cell-specific activation of the JCV promoter by Tax. Electrophoretic mobility shift assay demonstrated the presence of Tax-bound protein(s) that were specifically present in non-neuronal cells. This study is the first demonstration of the activation of JCV promoter by HTLV-I Tax in an NF-kappaB-dependent manner.
authors.affiliation: Laboratory of Molecular & Cellular Pathology, School of Medicine and Laboratory of Comparative Pathology, Graduate School of Veterinary Medicine, Hokkaido University, Kita-ku, Sapporo 060-8638, CREST, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Okada
authors.forename: H
authors.initials: H
authors.lastname: Sawa
authors.forename: S
authors.initials: S
authors.lastname: Tanaka
authors.forename: A
authors.initials: A
authors.lastname: Takada
authors.forename: S
authors.initials: S
authors.lastname: Suzuki
authors.forename: H
authors.initials: H
authors.lastname: Hasegawa
authors.forename: T
authors.initials: T
authors.lastname: Umemura
authors.forename: J
authors.initials: J
authors.lastname: Fujisawa
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: W W
authors.initials: WW
authors.lastname: Hall
authors.forename: K
authors.initials: K
authors.lastname: Nagashima
mesh_terms: D001483:Base Sequence; D017931:DNA Primers; D004279:DNA, Viral / Q000235:genetics; D016356:Gene Products, tax / Q000378:metabolism*; D006801:Humans; D007577:JC Virus / Q000235:genetics*; D009474:Neurons / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D017384:Sequence Deletion; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
chemical_list: D017931:DNA Primers; D004279:DNA, Viral; D016356:Gene Products, tax