Transmission and accumulation of CTL escape variants drive negative associations between HIV polymorphisms and HLA.
Transmission and accumulation of CTL escape variants drive negative associations between HIV polymorphisms and HLA.
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CTL逃生变体的传播和积累驱动HIV多态性与HLA之间的负相关。
DOI：
10.1084/jem.20041455
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发表时间：
2005-03-21
影响因子：
15.3
通讯作者：
Goulder, P
中科院分区：
文献类型：
--
作者：
Leslie, A;Kavanagh, D;Honeyborne, I;Pfafferott, K;Edwards, C;Pillay, T;Hilton, L;Thobakgale, C;Ramduth, D;Draenert, R;Le Gall, S;Luzzi, G;Edwards, A;Brander, C;Sewell, AK;Moore, S;Mullins, J;Moore, C;Mallal, S;Bhardwaj, N;Yusim, K;Phillips, R;Klenerman, P;Korber, B;Kiepiela, P;Walker, B;Goulder, P
人类免疫缺陷病毒 (HIV)-1 氨基酸序列多态性与特定人类组织相容性白细胞抗原 (HLA) I 类等位基因的表达相关，提示细胞毒性 T 淋巴细胞 (CTL) 介导的选择压力和免疫逃逸位点。最常观察到的关联是 HLA I 类分子的表达与共有序列的变异之间的关联。然而，已经鉴定出大量位点，其中特定的 HLA I 类等位基因表达与共有序列的保存相关。迄今为止，这背后的机制尚不清楚。目前的研究重点关注两个“负相关”或明显保留表位的例子，对这种现象提出了一种解释：负相关可能是由于逃逸突变的正选择而产生的，该突变在传播上是稳定的，因此在群体中积累到定义共有序列的程度。这种负面关联可能只是暂时存在，因为检测它们的统计能力随着突变的积累而减弱。如果逃逸变体在群体中固定下来，则该表位将失去作为免疫系统潜在目标的作用。这些数据有助于解释艾滋病毒在人群水平上如何演变。了解艾滋病毒进化的方向对于疫苗开发具有重要意义。
Human immunodeficiency virus (HIV)-1 amino acid sequence polymorphisms associated with expression of specific human histocompatibility leukocyte antigen (HLA) class I alleles suggest sites of cytotoxic T lymphocyte (CTL)-mediated selection pressure and immune escape. The associations most frequently observed are between expression of an HLA class I molecule and variation from the consensus sequence. However, a substantial number of sites have been identified in which particular HLA class I allele expression is associated with preservation of the consensus sequence. The mechanism behind this is so far unexplained. The current studies, focusing on two examples of “negatively associated” or apparently preserved epitopes, suggest an explanation for this phenomenon: negative associations can arise as a result of positive selection of an escape mutation, which is stable on transmission and therefore accumulates in the population to the point at which it defines the consensus sequence. Such negative associations may only be in evidence transiently, because the statistical power to detect them diminishes as the mutations accumulate. If an escape variant reaches fixation in the population, the epitope will be lost as a potential target to the immune system. These data help to explain how HIV is evolving at a population level. Understanding the direction of HIV evolution has important implications for vaccine development.
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影响因子：
64.8
作者：
Goulder, PJR;Brander, C;Walker, BD
通讯作者：
Walker, BD
影响因子：
5.4
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作者：
Goulder, PJR;Phillips, RE;RowlandJones, S
通讯作者：
RowlandJones, S