New CCR5 variants associated with reduced HIV coreceptor function in southeast Asia
New CCR5 variants associated with reduced HIV coreceptor function in southeast Asia
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DOI：
10.1097/00002030-200411190-00004
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发表时间：
2004-11-19
期刊：
影响因子：
3.8
通讯作者：
Theodorou, I
中科院分区：
文献类型：
--
作者：
Capoulade-Métay, C;Ma, LY;Theodorou, I
背景：尽管多次暴露于HIV-1，但仍有一些人未被感染。这种抗性与CCR 5受体基因中32个碱基对缺失的纯合性有关。目的：研究非白种人中CCR 5受体基因的变异对HIV感染易感性的影响。方法：对越南3组受试者进行CCR 5编码区多态性筛查，并与正常人进行比较。47名HIV-1感染的血管内吸毒者，50名HIV-1高度暴露但血清阴性的血管内吸毒者和37名HIV-1未暴露但血清阴性的个体。DNA进行了分析，通过变性高效液相色谱法，这是其次是检查的生化和HIV coreceptor特性的编码regions.Results：5 CCR 5编码区的变异被确定在这个越南人口。S185 R、1254 T和C269 F突变以前没有描述过; G106 R和R223 Q已经在其他亚洲人群中发现，但G106 R的功能特性尚不清楚。这些变体在生化和HIV辅助受体特性上不同。S185 R和1254 T变异体的受体和辅助受体活性与野生型相当，而C269 F和G106 R表现不同。后一对在细胞表面表达较差，与巨噬细胞炎性蛋白1 β（CCL 4）和RANTES（CCL 5）结合较弱，并显示HIV-1辅助受体效率降低。在越南人群中发现的五种CCR 5变体中，G106 R和C269 F显示出其受体和辅助受体特性的显著改变，这可能导致该人群对HIV-1感染的易感性和/或疾病进展。(C)2004年利平科特威廉姆斯威尔金斯。
Background: Despite multiple exposure to HIV-1, some individuals remain uninfected. This resistance has been associated with homozygosity for a 32 base pair deletion in the gene for the CCR5 receptor. This variant occurs frequently in Caucasians but is extremely rare in Asians or Africans.Objective: To identify variations in CCR5 receptor gene that affect susceptibility to HIV infection in non-Caucasians.Methods: CCR5 coding region polymorphisms were screened in three groups of Vietnamese subjects: 47 HIV-1 infected intravascular drug users, 50 highly HIV-1-exposed but seronegative intravascular drug users and 37 HIV-1-unexposed seronegative individuals. DNA was analysed by denaturing high performance liquid chromatography; this was followed by examination of the biochemical and HIV coreceptor properties of the coding regions.Results: Five CCR5 coding region variants were identified in this Vietnamese population. The S185R, 1254T and C269F mutations have not been previously described; G106R and R223Q have already been found in other Asian populations, but the functional properties of G106R is not known. These variants differed in biochemical and HIV coreceptor properties. S185R and 1254T variants had receptor and coreceptor activities comparable to that of the wild type, whereas C269F and G106R behaved differently. This latter pair are poorly expressed at the cell surface, weakly bind macrophage inflammatory protein 1beta (CCL4) and RANTES (CCL5), and display reduced HIV-1 coreceptor efficiency.Conclusions: Among the five CCR5 variants found in this Vietnamese population, G106R and C269F displayed significant modifications of their receptor and coreceptor properties, which may contribute to susceptibility to HIV-1 infection and/or disease progression within this population. (C) 2004 Lippincott Williams Wilkins.