Failure in activation of the canonical NF-κB pathway by human T-cell leukemia virus type 1 Tax in non-hematopoietic cell lines

Virology. 2013 Sep 1;443(2):226-35. doi: 10.1016/j.virol.2013.04.032. Epub 2013 Jun 18.

Abstract

Human T-cell leukemia virus type 1 (HTLV-1) Tax (Tax1) plays crucial roles in leukemogenesis in part through activation of NF-κB. In this study, we demonstrated that Tax1 activated an NF-κB binding (gpκB) site of the gp34/OX40 ligand gene in a cell type-dependent manner. Our examination showed that the gpκΒ site and authentic NF-κB (IgκB) site were activated by Tax1 in hematopoietic cell lines. Non-hematopoietic cell lines including hepatoma and fibroblast cell lines were not permissive to Tax1-mediated activation of the gpκB site, while the IgκB site was activated in those cells in association with binding of RelB. However RelA binding was not observed in the gpκB and IgκB sites. Our results suggest that HTLV-1 Tax1 fails to activate the canonical pathway of NF-κB in non-hematopoietic cell lines. Cell type-dependent activation of NF-κB by Tax1 could be associated with pathogenesis by HTLV-1 infection.

Keywords: Canonical pathway; HTLV-1; Hematopoietic cells; NF-κB; Tax1; Transcription.

MeSH terms

  • Cell Line
  • Gene Products, tax / metabolism*
  • HeLa Cells
  • Human T-lymphotropic virus 1 / genetics
  • Human T-lymphotropic virus 1 / metabolism
  • Human T-lymphotropic virus 1 / pathogenicity*
  • Humans
  • Jurkat Cells
  • Lymphocytes / virology*
  • NF-kappa B / chemistry
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • OX40 Ligand / genetics
  • OX40 Ligand / metabolism
  • Promoter Regions, Genetic
  • Receptors, OX40 / genetics
  • Receptors, OX40 / metabolism
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / metabolism
  • Transcriptional Activation*

Substances

  • Gene Products, tax
  • NF-kappa B
  • OX40 Ligand
  • RELA protein, human
  • Receptors, OX40
  • TNFRSF4 protein, human
  • TNFSF4 protein, human
  • Transcription Factor RelA
  • tax protein, Human T-lymphotrophic virus 1