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J. Biol. Chem., Vol. 275, Issue 22, 17016-17023, June 2, 2000
From the a Laboratory of Molecular & Cellular Pathology,
School of Medicine and b Laboratory of Comparative Pathology,
Graduate School of Veterinary Medicine, Hokkaido University, Kita-ku,
Sapporo 060-8638, c CREST, Japan Science and Technology,
f Department of Pathology, Sapporo Municipal Hospital, Chuo-ku,
Sapporo 060-8604, g Department of Infectious Pathology, National
Institute of Infectious Disease, Shinjuku-ku, Tokyo 162-0052, h Department of Microbiology, Kansai Medical University,
Fumizono-cho, Moriguchi, Osaka 570-8506, i Department of
Infectious Disease and Immunology, University of Ryukyu, Nishihara-cho,
Okinawa 903-0125, Japan, and j Department of Medical
Microbiology, Conway Institute of Biomolecular and Biomedical Research,
University College Dublin, Belfield, Dublin, Ireland
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-
Transcriptional Activation of JC Virus by Human T-lymphotropic
Virus Type I Tax Protein in Human Neuronal Cell Lines*
B-binding
motif could not be activated by Tax; 2) the overexpression of I
B
abolished Tax-induced transcriptional activation of the JCV promoter;
3) a Tax mutant (M22) lacking the potential for activation via the
NF-
B 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-
B-dependent manner.
*
This study was supported in part by grants from the Ministry
of Education, Science, Sports and Culture, Japan.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
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