Inactivation of HIV-1 chemokine co-receptor CXCR-4 by a novel intrakine strategy

Nat Med. 1997 Oct;3(10):1110-6. doi: 10.1038/nm1097-1110.


CXC-chemokine receptor (CXCR)-4/fusin, a newly discovered co-receptor for T-cell line (T)-tropic HIV-1 virus, plays a critical role in T-tropic virus fusion and entry into permissive cells. The occurrence of T-tropic HIV viruses is associated with CD4-positive cell decline and progression to AIDS, suggesting that the T-tropic HIV-1 contributes to AIDS pathogenesis. In this study, we used a novel strategy to inactivate CXCR-4 by targeting a modified CXC-chemokine to the endoplasmic reticulum (ER) to block the surface expression of newly synthesized CXCR-4. The genetically modified lymphocytes expressing this intracellular chemokine, termed "intrakine", are immune to T-tropic virus infection and appear to retain normal biological features. Thus, this genetic intrakine strategy is uniquely targeted at the conserved cellular receptor for the prevention of HIV-1 entry and may be developed into an effective treatment for HIV-1 infection and AIDS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome / therapy
  • B-Lymphocytes / immunology
  • Cell Line
  • Cell Line, Transformed
  • Cells, Cultured
  • Chemokine CXCL12
  • Chemokines / biosynthesis*
  • Chemokines, CXC*
  • Cytomegalovirus
  • Genetic Vectors
  • Giant Cells
  • HIV-1 / physiology*
  • HeLa Cells
  • Humans
  • Lymphocytes / immunology*
  • Polymerase Chain Reaction
  • Receptors, CXCR4 / antagonists & inhibitors*
  • Receptors, CXCR4 / biosynthesis
  • Receptors, CXCR4 / immunology
  • Receptors, HIV / antagonists & inhibitors*
  • Receptors, HIV / immunology
  • Recombinant Fusion Proteins / antagonists & inhibitors
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / immunology
  • Transfection
  • Tumor Cells, Cultured


  • CXCL12 protein, human
  • Chemokine CXCL12
  • Chemokines
  • Chemokines, CXC
  • Receptors, CXCR4
  • Receptors, HIV
  • Recombinant Fusion Proteins