DNA bar coding and pyrosequencing to identify rare HIV drug resistance mutations.
DNA bar coding and pyrosequencing to identify rare HIV drug resistance mutations.
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DOI：
10.1093/nar/gkm435
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发表时间：
2007
影响因子：
14.9
通讯作者：
Bushman FD
中科院分区：
文献类型：
--
作者：
Hoffmann C;Minkah N;Leipzig J;Wang G;Arens MQ;Tebas P;Bushman FD
接受抗逆转录病毒药物的HIV感染者选择抗药性突变体，导致经常治疗失败。病毒逃逸DNA条编码，我们能够平行地分析七个病毒群，总体表征118 093序列的平均长度103 bp的分析，表明抗药性突变是5％的人群。在患者的三个耐药艾滋病毒种群的样本中由于已经报道了四个额外的低丰度耐药性突变，其中一些会影响对抗逆转录病毒疗法的反应。在单个实验中，对许多HIV种群进行深入询问。
Treatment of HIV-infected individuals with antiretroviral agents selects for drug-resistant mutants, resulting in frequent treatment failures. Although the major antiretroviral resistance mutations are routinely characterized by DNA sequencing, treatment failures are still common, probably in part because undetected rare resistance mutations facilitate viral escape. Here we combined DNA bar coding and massively parallel pyrosequencing to quantify rare drug resistance mutations. Using DNA bar coding, we were able to analyze seven viral populations in parallel, overall characterizing 118 093 sequence reads of average length 103 bp. Analysis of a control HIV mixture showed that resistance mutations present as 5% of the population could be readily detected without false positive calls. In three samples of multidrug-resistant HIV populations from patients, all the drug-resistant mutations called by conventional analysis were identified, as well as four additional low abundance drug resistance mutations, some of which would be expected to influence the response to antiretroviral therapy. Methods for sensitive characterization of HIV resistance alleles have been reported, but only the pyrosequencing method allows all the positions at risk for drug resistance mutations to be interrogated deeply for many HIV populations in a single experiment.
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影响因子：
48
作者：
Cai, Fangping;Chen, Haifeng;Gao, Feng
通讯作者：
Gao, Feng
影响因子：
105.7
作者：
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Palmer, S;Kearney, M;Coffin, JM
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