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TY - JOUR AU - Samson, Michel AU - Libert, Frédérick AU - Doranz, Benjamin J. AU - Rucker, Joseph AU - Liesnard, Corinne AU - Farber, Claire-Michèle AU - Saragosti, Sentob AU - Lapouméroulie, Claudine AU - Cognaux, Jacqueline AU - Forceille, Christine AU - Muyldermans, Gaetan AU - Verhofstede, Chris AU - Burtonboy, Guy AU - Georges, Michel AU - Imai, Tsuneo AU - Rana, Shalini AU - Yi, Yanji AU - Smyth, Robert J. AU - Collman, Ronald G. AU - Doms, Robert W. AU - Vassart, Gilbert AU - Parmentier, Marc PY - 1996 DA - 1996/08/01 TI - Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene JO - Nature SP - 722 EP - 725 VL - 382 IS - 6593 AB - 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. SN - 1476-4687 UR - https://doi.org/10.1038/382722a0 DO - 10.1038/382722a0 ID - Samson1996 ER -