HLA and HIV-1:: Heterozygote advantage and B*35-Cw*04 disadvantage

被引:951
作者
Carrington, M
Nelson, GW
Martin, MP
Kissner, T
Vlahov, D
Goedert, JJ
Kaslow, R
Buchbinder, S
Hoots, K
O'Brien, SJ [1 ]
机构
[1] NCI, Lab Genom Divers, Frederick, MD 21702 USA
[2] NCI, Sci Applicat Corp Frederick, Intramural Res Support Program, Frederick, MD 21702 USA
[3] Johns Hopkins Sch Hyg & Publ Hlth, Baltimore, MD 21205 USA
[4] NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA
[5] Univ Alabama Birmingham, Multictr Hemophilia Cohort Study, Birmingham, AL 35294 USA
[6] San Francisco City Clin Cohort, San Francisco, CA 94102 USA
[7] Univ Texas, Hlth Sci Ctr, Gulf States Hemophilia Ctr, Houston, TX 77030 USA
关键词
D O I
10.1126/science.283.5408.1748
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
A selective advantage against infectious disease associated with increased heterozygosity at the human major histocompatibility complex [human Leukocyte antigen (HLA) class I and class II] is believed to play a major role in maintaining the extraordinary allelic diversity of these genes. Maximum HLA heterozygosity of class I loci (A, B, and C) delayed acquired immunodeficiency syndrome (AIDS) onset among patients infected with human immunodeficiency virus-type 1 (HIV-1), whereas individuals who were homozygous for one or more Loci progressed rapidly to AIDS and death. The HLA class I alleles B*35 and Cw*04 were consistently associated with rapid development of: AIDS-defining conditions in Caucasians. The extended survival of 28 to 40 percent of HIV1-infected Caucasian patients who avoided AIDS for ten or more years can be attributed to their being Fully heterozygous at HLA class I Loci, to their Lacking the AIDS-associated alleles B*35 and Cw*04, or to both.
引用
收藏
页码:1748 / 1752
页数:5
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