Evolution of sequences encoding the principal neutralization epitope of human immunodeficiency virus 1 is host dependent, rapid, and continuous.

Evolution of sequences encoding the principal neutralization epitope of human immunodeficiency virus 1 is host dependent, rapid, and continuous.
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编码人类免疫缺陷病毒1的主要中和表位的序列的进化是宿主依赖性的、快速且连续的。

DOI:
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发表时间:
1990
影响因子:
11.1
通讯作者:
Jaap Goudsmit
Jaap Goudsmit
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Tom F. W. Wolfs;JEAN;De;Jong;Henk Van Den;BERGt;J. M. Tijnagel;WillyJ.A. Krone;Jaap Goudsmit

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人免疫缺陷病毒1的主要中和表位位于外包膜的第三可变(V3)结构域,并已显示可结合分离株特异性抗体。因此,在直接从6名儿童及其血浆供体的外周血单核细胞获得的DNA中研究了编码该表位的核酸序列内的变异程度。这表明克隆后获得的序列的准种分布因受体而异,并且与供体序列的距离随着时间的推移而增加。V3核苷酸进化速率平均为9.5 × 10 - 3/位点/年(沉默位点)和11.4 × 10 - 3/位点/年(非沉默位点(与V3区5'附近的对照区相比,每个位点每年9.7和9.8 x 10(-3)),尽管观察到个体差异,与血清抗原水平或疾病进展无关。表位编码区本身(V3)和上游控制区的序列在未进展为AIDS的儿童中比在进展为AIDS的儿童中更多地偏离供体序列。V3序列的进化显然是宿主依赖性的,快速的,并且与抗原表达水平无关。
The principal neutralization epitope of human immunodeficiency virus 1 is localized in the third variable (V3) domain of the external envelope and has been shown to bind isolate-specific antibodies. Therefore, the extent of variation within the nucleic acid sequence encoding this epitope was studied in DNA directly obtained from peripheral blood mononuclear cells of six children and their plasma donor. This revealed that the quasi-species distribution of sequences obtained after cloning varied from recipient to recipient and that the distance from the donor sequences increased over time. V3 nucleotide evolution rates averaged 9.5 x 10(-3) per site per year for silent sites and 11.4 x 10(-3) per site per year for nonsilent sites (vs. 9.7 and 9.8 x 10(-3) per site per year for a control region 5' adjacent to the V3 region) and, although individual differences were observed, did not correlate with the serum antigen levels or disease progression. Sequences of both the epitope coding region itself (V3) and the control region upstream diverted more from the donor sequence among children not progressing to AIDS than among children progressing to AIDS. The evolution of V3 sequences is apparently host dependent, rapid, and independent of the level of antigen expression.