The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1

Nature. 1996 Aug 29;382(6594):833-5. doi: 10.1038/382833a0.

Abstract

A putative chemokine receptor that we previously cloned and termed LESTR has recently been shown to function as a co-receptor (termed fusin) for lymphocyte-tropic HIV-1 strains. Cells expressing CD4 became permissive to infection with T-cell-line-adapted HIV-1 strains of the syncytium-inducing phenotype after transfection with LESTR/fusin complementary DNA. We report here the indentification of a human chemokine of the CXC type, stromal cell-derived factor 1 (SDF-1), as the natural ligand for LESTR/fusin, and we propose the term CXCR-4 for this receptor, in keeping with the new chemokine-receptor nomenclature. SDF-1 activates Chinese hamster ovary (CHO) cells transfected with CXCR-4 cDNA as well as blood leukocytes and lymphocytes. In cell lines expressing CXCR-4 and CD4, and in blood lymphocytes, SDF-1 is a powerful inhibitor of infection by lymphocyte-tropic HIV-1 strains, whereas the CC chemokines RANTES, MIP-1 alpha and MIP-1 beta, which were shown previously to prevent infection with primary, monocyte-tropic viruses, are inactive. In combination with CC chemokines, which block the infection with monocyte/macrophage-tropic viruses, SDF-1 could help to decrease virus load and prevent the emergence of the syncytium-inducing viruses which are characteristic of the late stages of AIDS.

Publication types

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

MeSH terms

  • Animals
  • Anti-HIV Agents / metabolism
  • Anti-HIV Agents / pharmacology*
  • Binding, Competitive
  • CD4 Antigens / genetics
  • CD4 Antigens / metabolism
  • CHO Cells
  • Calcium / metabolism
  • Chemokine CCL4
  • Chemokine CCL5 / metabolism
  • Chemokine CXCL12
  • Chemokines / genetics
  • Chemokines / metabolism*
  • Chemokines / pharmacology*
  • Chemokines, CXC*
  • Cricetinae
  • Cricetulus
  • DNA, Viral / metabolism
  • HIV-1 / drug effects*
  • HIV-1 / metabolism
  • HeLa Cells
  • Humans
  • Leukocytes, Mononuclear / virology
  • Ligands
  • Macrophage Inflammatory Proteins / metabolism
  • Macrophages / virology
  • Membrane Fusion
  • Membrane Proteins / metabolism*
  • Molecular Sequence Data
  • Proviruses / genetics
  • Receptors, CXCR4
  • Receptors, HIV / metabolism*
  • Transfection

Substances

  • Anti-HIV Agents
  • CD4 Antigens
  • CXCL12 protein, human
  • Chemokine CCL4
  • Chemokine CCL5
  • Chemokine CXCL12
  • Chemokines
  • Chemokines, CXC
  • DNA, Viral
  • Ligands
  • Macrophage Inflammatory Proteins
  • Membrane Proteins
  • Receptors, CXCR4
  • Receptors, HIV
  • Calcium

Associated data

  • GENBANK/U16752