Wolfs T F, de Jong J J, Van den Berg H, Tijnagel J M, Krone W J, Goudsmit J
Human Retrovirus Laboratory, Academic Medical Centre, Amsterdam, The Netherlands.
Proc Natl Acad Sci U S A. 1990 Dec;87(24):9938-42. doi: 10.1073/pnas.87.24.9938.
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.
人类免疫缺陷病毒1型的主要中和表位定位于外膜的第三个可变（V3）结构域，并且已显示其能结合分离株特异性抗体。因此，我们研究了直接从六个儿童及其血浆供体的外周血单核细胞中获取的DNA中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接受者而异，并且与供体序列的差异程度随时间增加。V3核苷酸沉默位点的进化速率平均为每年每个位点9.5×10⁻³，非沉默位点为每年每个位点11.4×10⁻³（相比之下，V3区域5'端相邻的对照区域每年每个位点为9.7和9.8×10⁻³），并且尽管观察到个体差异，但与血清抗原水平或疾病进展无关。在未进展为艾滋病的儿童中，表位编码区本身（V3）和上游对照区的序列与供体序列的差异比进展为艾滋病的儿童更大。V3序列的进化显然依赖于宿主，速度很快，并且与抗原表达水平无关。
