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Letters to Nature
Nature 382, 722 - 725 (22 August 1996); doi:10.1038/382722a0

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

Michel Samson*, Frédérick Libert*, Benjamin J. Doranz, Joseph Rucker, Corinne Liesnard, Claire-Michèle Farber§, Sentob Saragosti, Claudine Lapouméroulie, Jacqueline Cognaux£, Christine Forceille£, Gaetan Muyldermans£, Chris Verhofstede£, Guy Burtonboy£, Michel Georgesstar, Tsuneo Imai**, Shalini Rana, Yanji Yi, Robert J. Smyth, Ronald G. Collman, Robert W. Doms, Gilbert Vassart* & Marc Parmentier*

* IRIBHN and Services de Génétique Médicale, Virologie and § Immunodéficiences, Université Libre de Bruxelles, Campus Erasme, 808 route de Lennik, B-1070 Bruxelles, Belgium Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA Institut Cochin de Génétique Moléculaire, Hôpital Cochin, 75014 Paris, France INSERM U120, Hôpital Robert Debré, 48 Bd Sérurier, 75935 Paris, France £ Belgian AIDS Reference Laboratories. star Department of Genetics, Faculty of Veterinary Medicine, University of Liège, Belgium ** Department of Surgery II, Nagoya University School of Medicine, Japan Pulmonary and Critical Care Division, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

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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