Higher selection pressure from antiretroviral drugs in vivo results in increased evolutionary distance in HIV-1 pol.
Higher selection pressure from antiretroviral drugs in vivo results in increased evolutionary distance in HIV-1 pol.
复制标题
体内抗逆转录病毒药物的较高选择压力导致 HIV-1 pol 的进化距离增加。
DOI：
10.1006/viro.1999.9774
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
D'aquila,RT
中科院分区：
文献类型：
--
作者：
Gunthard,HF;Leigh-Brown,AJ;D'Aquila,RT;Johnson,VA;Kuritzkes,DR;Richman,DD;Wong,JK;D'aquila,RT
我们研究了51名患者在转换到新的抗逆转录病毒联合逆转录酶（RT）抑制剂治疗后，选择压力对HIV-1 pol进化的影响。分别分析蛋白酶（PR）和RT阅读框的进化。计算从基线到第8周以及基线到第48周的序列之间的成对进化距离（ED）。对所有替换、同义替换和非同义替换分别计算ED。在第8周，当HIV RNA减少（选择压力）很高时，在RNA大量减少（强应答）的患者中，同义和非同义替换的pol差异明显增加。对PR和RT的单独分析显示，与无应答者相比，强应答者RT（在选择压力下）的ED显著增加，而两组中PR基因（在没有选择压力下）之间的差异没有差异。这种差异进化表明PR和RT在遗传上不相关，可能存在重组。ED在前8周迅速增加，随后在第48周只有微小的进一步上升，这表明预先存在的准种的选择解释了早期的变化。不成比例的大量同义替换解释了观察到的差异，并表明这种遗传变化可能不是完全沉默的。
We investigated the effect of selection pressures on evolution of HIV-1 pol in 51 patients after switching to a new antiretroviral combination reverse transcriptase (RT) inhibitor therapy. Evolution of the protease (PR) and RT reading frames were analysed separately. Pairwise evolutionary distances (ED) were calculated between sequences from baseline and week 8 and between baseline and week 48 of protocol therapy. ED were calculated for all substitutions and for synonymous and nonsynonymous substitutions separately. At week 8 when HIV RNA reduction (selection pressure) was high, significantly more divergence in pol in both synonymous and nonsynonymous substitutions was found in patients with substantial RNA reduction (strong responders). Separate analyses of PR and RT revealed significantly greater ED in the RT (under selection pressure) of strong compared with nonresponders, whereas divergence between PR genes (not under selection pressure) did not differ in those two groups. Such differential evolution indicates that PR and RT were genetically unlinked and suggests recombination. The rapid increase of ED over the first 8 weeks was followed by only a minimal further rise by week 48, suggesting that selection of preexisting quasispecies accounted for the early changes. A disproportionally high number of synonymous substitutions accounted for the observed divergence and indicated that such genetic changes may not be completely silent.
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DOI：
--
发表时间：
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期刊：
AIDS (London)
影响因子：
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作者：
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通讯作者：
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影响因子：
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