par Samson, M;Libert, Frédérick ;Doranz, Benjamin J.;Rucker, J;Liesnard, Corinne ;Farber, Claire ;Saragosti, S;Lapoumeroulie, C;Cognaux, J;Forceille, C;Muyldermans, G;Verhofstede, C;Burtonboy, Guy;Georges, M.;Imai, T;Rana, S;Yi, Y;Smyth, R J;Collman, R G;Doms, Robert W.;Vassart, Gilbert ;Parmentier, Marc
Référence Nature (London), 382, 6593, page (722-725)
Publication Publié, 1996-08
Référence Nature (London), 382, 6593, page (722-725)
Publication Publié, 1996-08
Article révisé par les pairs
Résumé : | 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 strains, and the orphan 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. |