Transcriptional activation of the intercellular adhesion molecule 1 (CD54) gene by human T lymphotropic virus types I and II Tax is mediated through a palindromic response element

AIDS Res Hum Retroviruses. 1997 Nov 1;13(16):1429-37. doi: 10.1089/aid.1997.13.1429.

Abstract

In vitro infection of T cells with human T lymphotropic virus types I and II (HTLV-I and HTLV-II) resulted in constitutive expression of ICAM-1. Higher levels of ICAM-1 mRNA were expressed in HTLV-transformed cell lines (MT-2, MoT, C8166) when compared with uninfected T cell lines (A301). We demonstrate that this activation is conferred through a site on the ICAM-1 promoter that is activated in trans by the Tax protein of HTLV-I and HTLV-II. Enhanced promoter activity was detected when the ICAM-1 construct (-1162/+1) was transfected into HTLV-I-infected (MT-2), HTLV-II-infected (MoT, AI 1050), or an HTLV-I Tax-only-expressing (C8166) cell line as compared to the uninfected T cell line (A3.01). Cotransfection of the uninfected T cell line A3.01 with the ICAM construct along with Tax-I and Tax-II expression plasmid also resulted in increased promoter activity. Furthermore, experiments with deletion constructs of the ICAM-1 promoter region indicated that a region between -88 and -53 bp relative to the transcription start site is sufficient for Tax-inducible CAT expression. This segment includes an 11-bp palindromic segment (TTTCCGGGAAA) that has homology with the IFN-gamma and IL-6 response element. An 11-bp segment containing this regulatory region proved to be sufficient to confer Tax-I and Tax-II inducibility on a heterologous promoter (TK-CAT). Taken together these findings indicate that constitutive expression of ICAM-1 by HTLV-infected cells is influenced by the viral trans-activator protein Tax. This increased expression of ICAM-1 in response to the Tax protein may play an important role in the lymphoproliferation associated with HTLV infection.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Line
  • Gene Expression Regulation
  • Gene Products, tax / genetics
  • Gene Products, tax / physiology*
  • Genes*
  • Genes, Regulator / genetics
  • Genes, Regulator / physiology*
  • Human T-lymphotropic virus 1 / genetics*
  • Human T-lymphotropic virus 2 / genetics*
  • Humans
  • Intercellular Adhesion Molecule-1 / genetics*
  • Intercellular Adhesion Molecule-1 / physiology*
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology
  • Promoter Regions, Genetic / genetics
  • Promoter Regions, Genetic / physiology
  • RNA, Messenger / genetics
  • RNA, Messenger / physiology
  • Regulatory Sequences, Nucleic Acid / genetics
  • Regulatory Sequences, Nucleic Acid / physiology
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / virology*
  • Transcriptional Activation*

Substances

  • Gene Products, tax
  • Membrane Proteins
  • RNA, Messenger
  • Intercellular Adhesion Molecule-1