HLA and HIV-1:: Heterozygote advantage and B*35-Cw*04 disadvantage
HLA and HIV-1:: Heterozygote advantage and B*35-Cw*04 disadvantage
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DOI：
10.1126/science.283.5408.1748
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发表时间：
1999-03-12
期刊：
影响因子：
56.9
通讯作者：
O'Brien, SJ
中科院分区：
文献类型：
--
作者：
Carrington, M;Nelson, GW;O'Brien, SJ
与人类主要组织相容性复合体[人类白细胞抗原（HLA）I类和II类]杂合性增加相关的对感染性疾病的选择性优势被认为在维持这些基因的非凡等位基因多样性方面发挥主要作用。在感染人类免疫缺陷病毒1型（HIV-1）的患者中，I类基因座（A、B和C）的最大HLA杂合性延迟了获得性免疫缺陷综合征（AIDS）的发病，而一个或多个基因座纯合的个体则迅速进展为AIDS和死亡。HLA I类等位基因B*35和Cw*04始终与以下疾病的快速发展相关：白种人的艾滋病定义疾病。28%~ 40%的HIV 1感染的白种人患者在避免艾滋病10年或更长时间后存活时间延长，这可归因于他们在HLA I类基因座上是完全杂合的，或归因于他们缺乏与艾滋病相关的等位基因B*35和Cw*04，或归因于两者。
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.