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Abstract

HIV-1 and related viruses require co-receptors, in addition to CD4, to infect target cells. The chemokine receptor CCR-5 (ref. 1) was recently demonstrated to be a co-receptor for macrophage-tropic (M-tropic) HIV-1 strains2–6, and the orphan7 receptor LESTR (also called fusin) allows infection by strains adapted for growth in transformed T-cell lines (T-tropic strains). Here we show that a mutant allele of CCR-5 is present at a high frequency in caucasian populations (allele frequency, 0.092), but is absent in black populations from Western and Central Africa and Japanese populations. A 32-base-pair deletion within the coding region results in a frame shift, and generates a non-functional receptor that does not support membrane fusion or infection by macrophage- and dual-tropic HIV-1 strains. In a cohort of HIV-1-infected caucasian subjects, no individual homozygous for the mutation was found, and the frequency of heterozygotes was 35% lower than in the general population. White blood cells from an individual homozygous for the null allele were found to be highly resistant to infection by M-tropic HIV-1 viruses, confirming that CCR-5 is the major co-receptor for primary HIV-1 strains. The lower frequency of heterozygotes in seropositive patients may indicate partial resistance.

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Affiliations

  1. IRIBHN, Université Libre de Bruxelles, Campus Erasme, 808 route de Lennik, B-1070 Bruxelles, Belgium

    • Michel Samson
    • , Frédérick Libert
    • , Gilbert Vassart
    •  & Marc Parmentier
  2. Services de Génétique Médicale, Université Libre de Bruxelles, Campus Erasme, 808 route de Lennik, B-1070 Bruxelles, Belgium

    • Gilbert Vassart
  3. Services de Virologie, Université Libre de Bruxelles, Campus Erasme, 808 route de Lennik, B-1070 Bruxelles, Belgium

    • Corinne Liesnard
  4. Services de Immunodéficiences, Université Libre de Bruxelles, Campus Erasme, 808 route de Lennik, B-1070 Bruxelles, Belgium

    • Claire-Michèle Farber
  5. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA

    • Benjamin J. Doranz
    • , Joseph Rucker
    •  & Robert W. Doms
  6. Institut Cochin de Génétique Moléculaire, Hôpital Cochin, 75014 Paris, France

    • Sentob Saragosti
  7. INSERM U120, Hôpital Robert Debré, 48 Bd Sérurier, 75935 Paris, France

    • Claudine Lapouméroulie
  8. Belgian AIDS Reference Laboratories.

    • Jacqueline Cognaux
    • , Christine Forceille
    • , Gaetan Muyldermans
    • , Chris Verhofstede
    •  & Guy Burtonboy
  9. Department of Genetics, Faculty of Veterinary Medicine, University of Liège, Belgium

    • Michel Georges
  10. Department of Surgery II, Nagoya University School of Medicine, Japan

    • Tsuneo Imai
  11. Pulmonary and Critical Care Division, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    • Shalini Rana
    • , Yanji Yi
    • , Robert J. Smyth
    •  & Ronald G. Collman

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https://doi.org/10.1038/382722a0

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