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

• Published in: Nature (London) Vol. 382; no. 6593; pp. 722 - 725
• Main Authors: Samson, Michel, Libert, Frédérick, Doranz, Benjamin J, Rucker, Joseph, Liesnard, Corinne, Farber, Claire-Michèle, Saragosti, Sentob, Lapouméroulie, 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 22.08.1996; Nature Publishing Group
• Subjects: AIDS/HIV; Alleles; Amino Acid Sequence; Base Sequence; Biological and medical sciences; Cloning, Molecular; Cohort Studies; DNA Primers; European Continental Ancestry Group - genetics; Frameshift Mutation; Fundamental and applied biological sciences. Psychology; Gene Frequency; Genetics; Genotype; HIV; HIV Infections - genetics; HIV Infections - immunology; HIV Seropositivity - genetics; HIV Seropositivity - immunology; HIV-1 - immunology; Human immunodeficiency virus; human immunodeficiency virus 1; Humans; Immunity, Innate - genetics; Immunity, Innate - immunology; Medical research; Membrane Fusion; Microbiology; Molecular Sequence Data; Mutation; Polymerase Chain Reaction; Protein Conformation; Receptors, CCR5; Receptors, Cytokine - chemistry; Receptors, Cytokine - genetics; Receptors, Cytokine - immunology; Receptors, HIV - chemistry; Receptors, HIV - genetics; Receptors, HIV - immunology; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; Virology; Viruses; Human; HIV-1 virus; Cytokine; Retroviridae; Host virus relation; Chemotactic factor; Virus; Resistance; Lentivirinae; Human immunodeficiency virus; Mutation; Caucasoid; Biological receptor
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/382722a0

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.