Mechanism of the gene expression of HTLV-I and its association with ATL

AIDS Res. 1986 Dec:2 Suppl 1:S71-8.

Abstract

Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia (ATL) and a trans-acting viral function was proposed to be involved in ATL development because of the non-specific provirus integration in leukemic cells and the frequent immortalization of helper T-cells by in vitro infection. An extra sequence "pX" in the HTLV-1 genome codes for three proteins, p40x-, p27x- and p21x-, and the p40x- is trans-activator of transcription from the viral LTR. A sequence of 21 bp repeats in the LTR was found to be an enhancer and respond to the trans-activation by p40x-. The transient expression of p40x- also activates a cellular gene for interleukin 2 receptor (IL-2R) in helper T-cell lines. This induction of IL-2R may explain the mechanism of preferential growth of HTLV-1 infected cells and may be an early event of ATL development. For practical purposes, the env gene fragments was expressed in E. coli as fusion proteins with beta-galactosidase. Using these fusion proteins, a diagnostic system detecting anti-env antibodies was developed. Immunization of monkeys with these envelope-fusion proteins protected the monkeys from the viral infection, suggesting possible usage of envelope proteins as vaccine.

MeSH terms

  • Animals
  • Cell Transformation, Viral
  • Deltaretrovirus / genetics*
  • Deltaretrovirus / pathogenicity
  • Gene Expression Regulation*
  • Genes
  • Genes, Viral
  • Haplorhini
  • Humans
  • Leukemia / etiology*
  • Rabbits
  • Receptors, Immunologic / biosynthesis
  • Receptors, Immunologic / genetics
  • Receptors, Interleukin-2
  • Recombinant Fusion Proteins / immunology
  • Repetitive Sequences, Nucleic Acid
  • Retroviridae Proteins / biosynthesis
  • Retroviridae Proteins / genetics*
  • Retroviridae Proteins / physiology
  • T-Lymphocytes
  • Trans-Activators
  • Transcription, Genetic
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology
  • Viral Vaccines / immunology
  • Viral Vaccines / isolation & purification

Substances

  • Receptors, Immunologic
  • Receptors, Interleukin-2
  • Recombinant Fusion Proteins
  • Retroviridae Proteins
  • Trans-Activators
  • Viral Envelope Proteins
  • Viral Vaccines