Selection analyses of paired HIV-1 gag and gp41 sequences obtained before and after antiretroviral therapy.
Selection analyses of paired HIV-1 gag and gp41 sequences obtained before and after antiretroviral therapy.
复制标题
对抗逆转录病毒治疗前后获得的配对 HIV-1 gag 和 gp41 序列进行选择分析。
DOI：
10.1038/sdata.2018.147
复制
发表时间：
2018
期刊：
影响因子：
9.8
通讯作者：
Shafer,RobertW
中科院分区：
文献类型：
--
作者：
Tzou,PhilipL;Rhee,Soo-Yon;Pond,SergeiLKosakovsky;Manasa,Justen;Shafer,RobertW
大多数HIV-1感染者在使用药理学增强的蛋白酶抑制剂（PI）方案时病毒学失败，不会发生PI耐药蛋白酶突变。一种提出的解释是，HIV-1 gag或gp 41胞质结构域突变也可能降低PI易感性。在最近的一项研究中，配对的gag和gp 41序列的个人与病毒学失败的PI方案，我们没有确定PI选择的突变，并得出结论，如果这样的突变存在，将需要大量的配对序列从多个研究，他们的鉴定。在这项研究中，我们分别使用来自5，338和4，242名ART初治个体的gag和gp 41发表序列生成了位点特异性氨基酸谱，以帮助研究人员识别治疗期间出现的异常突变，并为配对序列中dN/dS置换率的确定和新的最大似然估计提供脚本。用于生成策展序列、氨基酸谱和dN/dS分析的管道将有助于将一致的方法应用于配对的gag和gp 41序列数据集，并加快在PI选择压力下识别潜在位点。
Most HIV-1-infected individuals with virological failure on a pharmacologically-boosted protease inhibitor (PI) regimen do not develop PI-resistance protease mutations. One proposed explanation is that HIV-1 gag or gp41 cytoplasmic domain mutations might also reduce PI susceptibility. In a recent study of paired gag and gp41 sequences from individuals with virological failure on a PI regimen, we did not identify PI-selected mutations and concluded that if such mutations existed, larger numbers of paired sequences from multiple studies would be needed for their identification. In this study, we generated site-specific amino acid profiles using gag and gp41 published sequences from 5,338 and 4,242 ART-naïve individuals, respectively, to assist researchers identify unusual mutations arising during therapy and to provide scripts for performing established and novel maximal likelihood estimates of dN/dS substitution rates in paired sequences. The pipelines used to generate the curated sequences, amino acid profiles, and dN/dS analyses will facilitate the application of consistent methods to paired gag and gp41 sequence datasets and expedite the identification of potential sites under PI-selection pressure.