Accurate reconstruction of a known HIV-1 transmission history by phylogenetic tree analysis
Accurate reconstruction of a known HIV-1 transmission history by phylogenetic tree analysis
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DOI：
10.1073/pnas.93.20.10864
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发表时间：
1996-10-01
影响因子：
11.1
通讯作者：
Albert, J
中科院分区：
文献类型：
--
作者：
Leitner, T;Escanilla, D;Albert, J
系统发育分析越来越多地用于试图澄清人类免疫缺陷病毒1型（HIV-1）的传播模式，但关于其有效性的讨论仍在继续，因为较小的HIV变异体的趋同进化和传播可能会掩盖流行病学模式，在这里，我们研究了一个独特的HIV-1传播集群，由9个感染个体组成，对他们来说，每一次病毒传播的时间和方向都是准确的。本研究从未培养的淋巴细胞中直接测定了HIV-1基因组p17 gag和env V3区的序列，并根据传播发生的时间和样品获得的时间，构建了一个真实的系统发育树。将已知的HIV-1传播史与重建的分子树进行比较，重建的分子树是通过几种常用的系统发育推断方法[Fitch-Margoliash、邻接、最小进化、最大似然、最大简约、使用算术平均的未加权对组方法（UPGMA）和假设分子钟的Fitch-Margoliash方法（KITSCH）]从DNA序列计算的。大多数重建的树木是真实的繁殖力的良好估计; 13个分类群中有12个被正确地定位在最精确的树中，发现基因片段的选择比系统发育方法和替代模型的选择更重要，但对不等变化率敏感的方法表现较差（如UPGMA和KITSCH，它们假定恒定的分子钟），快速进化的V3片段比p17给出更好的重建，但p17和V3的组合数据集表现最好，系统发育方法的准确性证明了它们在HIV-1研究中的使用，并反对某些病毒变体的趋同进化和选择性传播。
Phylogenetic analyses are increasingly used in attempts to clarify transmission patterns of human immunodeficiency virus type 1 (HIV-1), but there is a continuing discussion about their validity because convergent evolution and transmission of minor HIV variants may obscure epidemiological patterns, Here we have studied a unique HIV-1 transmission cluster consisting of nine infected individuals, for whom the time and direction of each virus transmission was exactly known. Most of the transmissions occurred between 1981 and 1983, and a total of 13 blood samples were obtained approximately 2-12 years later, The p17 gag and env V3 regions of the HIV-1 genome were directly sequenced from uncultured lymphocytes, A true phylogenetic tree was constructed based on the knowledge about when the transmissions had occurred and when the samples were obtained, This complex, known HIV-1 transmission history was compared with reconstructed molecular trees, which were calculated from the DNA sequences by several commonly used phylogenetic inference methods [Fitch-Margoliash, neighbor-joining, minimum-evolution, maximum-likelihood, maximum-parsimony, unweighted pair group method using arithmetic averages (UPGMA), and a Fitch-Margoliash method assuming a molecular clock (KITSCH)]. A majority of the reconstructed trees were good estimates of the true phylogeny; 12 of 13 taxa were correctly positioned in the most accurate trees, The choice of gene fragment was found to be more important than the choice of phylogenetic method and substitution model, However, methods that are sensitive to unequal rates of change performed more poorly (such as UPGMA and KITSCH, which assume a constant molecular clock), The rapidly evolving V3 fragment gave better reconstructions than p17, but a combined data set of both p17 and V3 performed best, The accuracy of the phylogenetic methods justifies their use in HIV-1 research and argues against convergent evolution and selective transmission of certain virus variants.