Molecular footprint of drug-selective pressure in a human immunodeficiency virus transmission chain
Molecular footprint of drug-selective pressure in a human immunodeficiency virus transmission chain
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DOI：
10.1128/jvi.79.18.11981-11989.2005
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发表时间：
2005-09-01
影响因子：
5.4
通讯作者：
Vandamme, AM
中科院分区：
文献类型：
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作者：
Lemey, P;Derdelinckx, I;Vandamme, AM
已知的人类免疫缺陷病毒（HIV）的传播历史是非常宝贵的模型，用于调查病毒的进化和传播动力学，并评估系统发育重建的准确性。在这里，我们描述了一个由9名感染者组成的HIV-1传播链，几乎所有人都在感染后期接受了抗病毒药物治疗。HIV基因组的部分pol和env gp 41区域直接从每个患者的至少一个样品的血浆病毒RNA测序。系统发育分析在波尔使用可能性方法推断的进化历史不完全兼容与已知的传输历史。这可能是由于耐药突变的平行进化导致多重耐药病毒的不正确聚类。另一方面，一个完全兼容的系统发育树重建从env序列。我们能够确定和量化的分子足迹的药物选择性压力在波尔使用最大似然推断不同的密码子取代模型。使用分子钟模型证明了多药耐药患者的HIV人群中突变固定率增加。我们表明，分子进化分析，由已知的传播历史的指导下，可以揭示存在的混淆因素，如自然选择和谨慎时，应采取准确的描述艾滋病毒的进化是必需的。
Known human immunodeficiency virus (HIV) transmission histories are invaluable models for investigating the evolutionary and transmission dynamics of the virus and to assess the accuracy of phylogenetic reconstructions. Here we have characterized an HIV-1 transmission chain consisting of nine infected patients, almost all of whom were treated with antiviral drugs at later stages of infection. Partial pol and env gp41 regions of the HIV genome were directly sequenced from plasma viral RNA for at least one sample from each patient. Phylogenetic analyses in pol using likelihood methods inferred an evolutionary history not fully compatible with the known transmission history. This could be attributed to parallel evolution of drug resistance mutations resulting in the incorrect clustering of multidrug-resistant virus. On the other hand, a fully compatible phylogenetic tree was reconstructed from the env sequences. We were able to identify and quantify the molecular footprint of drug-selective pressure in pol using maximum likelihood inference under different codon substitution models. An increased fixation rate of mutations in the HIV population of the multidrug-resistant patient was demonstrated using molecular clock modeling. We show that molecular evolutionary analyses, guided by a known transmission history, can reveal the presence of confounding factors like natural selection and caution should be taken when accurate descriptions of HIV evolution are required.