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The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry

Nature volume 382, pages 829–833 (1996)Cite this article

Abstract

CHEMOKINES are chemotactic cytokines that activate and direct the migration of leukocytes1,2. There are two subfamilies, the CXC and the CC chemokines. We recently found that the CXC-chemokine stromal cell-derived factor-1 (SDF-1)3,4 is a highly efficacious lymphocyte chemoattractant5. Chemokines act on responsive leukocyte subsets through G-protein-coupled seven-transmembrane receptors1, which are also used by distinct strains of HIV-1 as cofactors for viral entry. Laboratory-adapted and some T-celi-line-tropic (T-tropic) primary viruses use the orphan chemokine receptor LESTR/fusin (also known as fusin)6–8, whereas macrophage-tropic primary HIV-1 isolates use CCR-5 and CCR-3 (refs 7–11), which are receptors for known CC chemokines. Testing of potential receptors demonstrated that SDF-1 signalled through, and hence 'adopted', the orphan receptor LESTR, which we therefore designate CXC-chemokine receptor-4 (CXCR-4). SDF-1 induced an increase in intracellular free Ca2+ and chemotaxis in CXCR-4-transfected cells. Because SDF-1 is a biological ligand for the HIV-1 entry cofactor LESTR, we tested whether it inhibited HIV-1. SDF-1 inhibited infection by T-tropic HIV-1 of HeLa-CD4 cells, CXCR-4 transfectants, and peripheral blood mononuclear cells (PBMCs), but did not affect CCR-5-mediated infection by macrophage-tropic (M-tropic) and dual-tropic primary HIV-1.

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Affiliations

  1. The Center for Blood Research, Dana-Farber Cancer Institute, Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts, 02115, USA

    Conrad C. Bleul & Timothy A. Springer

  2. Division of Human Retrovirology, Dana-Farber Cancer Institute, Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts, 02115, USA

    Michael Farzan, Hyeryun Choe, Cristina Parolin & Joseph Sodroski

  3. Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts, 02115, USA

    Joseph Sodroski

  4. Institute of Microbiology, University of Padua, Padua, 35121, Italy

    Cristina Parolin

  5. Biomedical Research Centre, University of British Columbia, 2222 Health Sciences Mall, Vancouver, British Columbia, V6T 1Z3, Canada

    Ian Clark-Lewis

Authors
  1. Conrad C. Bleul
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  2. Michael Farzan
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  3. Hyeryun Choe
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  4. Cristina Parolin
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  5. Ian Clark-Lewis
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  6. Joseph Sodroski
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  7. Timothy A. Springer
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Bleul, C., Farzan, M., Choe, H. et al. The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry. Nature 382, 829–833 (1996). https://doi.org/10.1038/382829a0

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