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: Y Okada, H Sawa, S Tanaka, A Takada, S Suzuki, H Hasegawa, T Umemura, J Fujisawa, Y Tanaka, W W Hall, K Nagashima
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 275 Issue 22 Pg. 17016-23 (Jun 02 2000) ISSN: 0021-9258 [Print] United States
• PMID: 10828075 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Primers
• DNA, Viral
• Gene Products, tax

Topics

• Base Sequence
• DNA Primers
• DNA, Viral (genetics)
• Gene Products, tax (metabolism)
• Humans
• JC Virus (genetics)
• Neurons (metabolism)
• Promoter Regions, Genetic
• Sequence Deletion
• Transcriptional Activation
• Tumor Cells, Cultured