Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene (original) (raw)

• Letter
• Published: 22 August 1996
• Frédérick Libert1,
• Benjamin J. Doranz5,
• Joseph Rucker5,
• Corinne Liesnard3,
• Claire-Michèle Farber4,
• Sentob Saragosti6,
• Claudine Lapouméroulie7,
• Jacqueline Cognaux8,
• Christine Forceille8,
• Gaetan Muyldermans8,
• Chris Verhofstede8,
• Guy Burtonboy8,
• Michel Georges9,
• Tsuneo Imai10,
• Shalini Rana11,
• Yanji Yi11,
• Robert J. Smyth11,
• Ronald G. Collman11,
• Robert W. Doms5,
• Gilbert Vassart1,2 &
• …
• Marc Parmentier1

Nature volume 382, pages 722–725 (1996)Cite this article

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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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Authors and 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

Authors

1. Michel Samson
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2. Frédérick Libert
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3. Benjamin J. Doranz
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4. Joseph Rucker
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5. Corinne Liesnard
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6. Claire-Michèle Farber
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7. Sentob Saragosti
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8. Claudine Lapouméroulie
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9. Jacqueline Cognaux
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10. Christine Forceille
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11. Gaetan Muyldermans
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12. Chris Verhofstede
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13. Guy Burtonboy
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14. Michel Georges
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15. Tsuneo Imai
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16. Shalini Rana
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17. Yanji Yi
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18. Robert J. Smyth
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19. Ronald G. Collman
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20. Robert W. Doms
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21. Gilbert Vassart
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22. Marc Parmentier
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Samson, M., Libert, F., Doranz, B. et al. Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene.Nature 382, 722–725 (1996). https://doi.org/10.1038/382722a0

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• Received: 17 July 1996
• Accepted: 06 August 1996
• Issue Date: 22 August 1996
• DOI: https://doi.org/10.1038/382722a0

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