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

被引:2309
作者
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
机构
[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
[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
关键词
D O I
10.1038/382722a0
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:722 / 725
页数:4
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