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J. Biol. Chem., Vol. 275, Issue 22, 17016-17023, June 2, 2000
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Transcriptional Activation of JC Virus by Human T-lymphotropic Virus Type I Tax Protein in Human Neuronal Cell Lines*

Yuki Okadaabcd, Hirofumi Sawaace, Shinya Tanakaac, Akio Takadaf, Satoko Suzukiac, Hideki Hasegawacg, Takashi Umemurab, Jun-ichi Fujisawah, Yuetsu Tanakai, William W. Halljk, and Kazuo Nagashimaac

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-kappa B-binding motif could not be activated by Tax; 2) the overexpression of Ikappa Balpha abolished Tax-induced transcriptional activation of the JCV promoter; 3) a Tax mutant (M22) lacking 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 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-kappa 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.

d Research Fellow of the Japan Society for the promotion of Science.

e To whom correspondence should be addressed: Laboratory of Molecular and Cellular Pathology, Hokkaido University School of Medicine, N15, W7, Kita-ku, Sapporo 060-8638, Japan. Tel: 81-11-706-5053; Fax: 81-11-706-7806; E-mail: h-sawa@patho2.med.hokudai.ac.jp.

k Supported by the Japanese Foundation for AIDS Prevention.


Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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