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| Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene |
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| Author(s): Samson M, Libert F, Doranz BJ, Rucker J, Liesnard C, Farber CM, Saragosti S, Lapoumeroulie C, Cognaux J, Forceille C, Muyldermans G, Verhofstede C, Burtonboy G, Georges M, Imai T, Rana S, Yi YJ, Smyth RJ, Collman RG, Doms RW, Vassart G, Parmentier M |
| Source: NATURE Volume: 382 Issue: 6593 Pages: 722-725 Published: AUG 22 1996 |
| Times Cited: 1,491 References: 24 |
| Abstract: 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(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 cc-receptor for primary HIV-1 strains, The lower frequency of heterozygotes in seropositive patients may indicate partial resistance. |
| Document Type: Article |
| Language: English |
Addresses:
1. FREE UNIV BRUSSELS, IRIBHN, B-1070 BRUSSELS, BELGIUM
2. FREE UNIV BRUSSELS, SERV GENET MED, B-1070 BRUSSELS, BELGIUM
3. FREE UNIV BRUSSELS, SERV VIROL, B-1070 BRUSSELS, BELGIUM
4. FREE UNIV BRUSSELS, SERV IMMUNODEFICIENCES, B-1070 BRUSSELS, BELGIUM
5. UNIV PENN, DEPT PATHOL & LAB MED, PHILADELPHIA, PA 19104 USA
6. HOP COCHIN, INST COCHIN GENET MOL, F-75014 PARIS, FRANCE
7. HOP ROBERT DEBRE, INSERM, U120, F-75935 PARIS, FRANCE
8. UNIV LIEGE, BELGIAN AIDS REFERENCE LABS, B-4000 LIEGE, BELGIUM
9. UNIV LIEGE, FAC VET MED, DEPT GENET, B-4000 LIEGE, BELGIUM
10. NAGOYA UNIV, SCH MED, DEPT SURG 2, NAGOYA, AICHI 466 JAPAN
11. UNIV PENN, DEPT MED, DIV PULM & CRIT CARE, PHILADELPHIA, PA 19104 USA |
| Publisher: MACMILLAN MAGAZINES LTD, 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: VD333 |
| ISSN: 0028-0836 |
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