Selective elimination of HIV-1-infected cells with an interleukin-2 receptor-specific cytotoxin

Science. 1991 Jun 21;252(5013):1703-5. doi: 10.1126/science.1904628.

Abstract

Infection by human immunodeficiency virus type 1 (HIV-1) is associated with cellular activation and expression of the interleukin-2 (IL-2) receptor. A genetically engineered fusion toxin, DAB486 IL-2, that contains the enzymatic site and translocation domain of diphtheria toxin and the receptor binding domain of IL-2 specifically kills cells that express high-affinity IL-2 receptors. This toxin selectively eliminated the HIV-1-infected cells from mixed cultures of infected and uninfected cells and inhibited production of viral proteins and infectious virus. Thus, cellular activation antigens present a target for early antiviral intervention.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Survival
  • Diphtheria Toxin / administration & dosage*
  • Diphtheria Toxin / genetics
  • Gene Products, env / metabolism
  • Gene Products, gag / metabolism
  • HIV Core Protein p24
  • HIV Envelope Protein gp160
  • HIV Infections / therapy*
  • HIV-1 / metabolism
  • Humans
  • In Vitro Techniques
  • Interleukin-2 / genetics
  • Interleukin-2 / metabolism
  • Protein Precursors / metabolism
  • Receptors, Interleukin-2 / physiology*
  • Recombinant Fusion Proteins / toxicity
  • T-Lymphocytes / cytology
  • T-Lymphocytes / microbiology*
  • Viral Core Proteins / metabolism

Substances

  • Diphtheria Toxin
  • Gene Products, env
  • Gene Products, gag
  • HIV Core Protein p24
  • HIV Envelope Protein gp160
  • Interleukin-2
  • Protein Precursors
  • Receptors, Interleukin-2
  • Recombinant Fusion Proteins
  • Viral Core Proteins
  • p55 gag precursor protein, Human immunodeficiency virus 1