Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene.
Samson, Michel; Libert, Frederick; Doranz, Benjamin J.; Rucker, Joseph; Liesnard, Corinne; Farber, Claire-Michele; Saragosti, Sentob; Lapoumeroulie, Claudine; Cognaux, Jacqueline; Forceille, Christine; Muyldermans, Gaetan; Verhofstede, Chris; Burtonboy, Guy; Georges, Michel; Imai, Tsuneo; Rana, Shalini; Yi, Yanji; Smyth, Robert J.; Collman, Ronald G.; Doms, Robert W.; Vassart, Gilbert; Parmentier, Marc
[Letter] Nature. 382(6593):722-725, August 22, 1996.

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HIV-1 and related viruses require co-receptors, in addition to CD4, to infect target cells. The chemokine receptor CCR-5 ( [1]) was recently demonstrated to be a co-receptor for macrophage-tropic (M-tropic) HIV-1 strains [2-6], and the orphan [7] 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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