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 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.
Okada
Y
Y
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.
Sawa
H
H
Tanaka
S
S
Takada
A
A
Suzuki
S
S
Hasegawa
H
H
Umemura
T
T
Fujisawa
J
J
Tanaka
Y
Y
Hall
W W
WW
Nagashima
K
K
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
D017931:DNA Primers; D004279:DNA, Viral; D016356:Gene Products, tax