Transcriptional activation of JC virus by human T-lymphotropic virus type I Tax protein in human neuronal cell lines

J Biol Chem. 2000 Jun 2;275(22):17016-23. doi: 10.1074/jbc.275.22.17016.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

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