São Paulo State University (Unesp), Medical School, Botucatu, Sao Paulo State, Brazil.
São Paulo State University (Unesp), School of Agriculture (FCA), Department of Bioprocess and Biotechnology, Botucatu, Sao Paulo State, Brazil.
Sci Rep. 2018 May 29;8(1):8280. doi: 10.1038/s41598-018-26675-z.
Variability of the HIV reverse transcriptase (RT) and protease (PR) genes has been used as indicators of drug resistance and as a mean to evaluate phylogenetic relationships among circulating virus. However, these studies have been carried in HIV mono-infected populations. The goal of this study was to evaluate, for the first time, the HIV PR and RT sequences from HIV/HBV and HIV/HCV co-infected patients. HIV PR and RT genes were amplificated and sequenced to resistance analysis. The bioinformatics analysis was performed to infer about sequences clustering and molecular evolution. The results showed that the most frequent amino acid substitutions in RT were L214F (67.6%), I135T (55.9%), and in PR was V15I (41.2%). The molecular clock analysis showed that the HIV circulating in co-infected patients were separated in two clusters in the years 1999-2000. Some patients included as HIV mono-infected according patients' medical records and inside the co-infected cluster were, in fact, co-infected by PCR analysis. Analysis of the decision trees showed susceptibility to lamivudine and emtricitabine were important attribute to characterize co-infected patients. In conclusion, the results obtained in this study suggest, for the first time, that HIV RT and PR genes variability could be a genetic biomarker to coinfection.
HIV 逆转录酶 (RT) 和蛋白酶 (PR) 基因的变异性已被用作耐药性的指标,并作为评估循环病毒种系发生关系的一种手段。然而,这些研究仅在 HIV 单一感染人群中进行。本研究的目的是首次评估 HIV/HBV 和 HIV/HCV 合并感染患者的 HIV PR 和 RT 序列。扩增和测序 HIV PR 和 RT 基因以进行耐药性分析。进行生物信息学分析以推断序列聚类和分子进化。结果表明,RT 中最常见的氨基酸取代是 L214F(67.6%)、I135T(55.9%),PR 中是 V15I(41.2%)。分子钟分析表明,1999-2000 年间,合并感染患者体内的 HIV 病毒在两个集群中分离。根据患者病历和合并感染集群中包含的一些被归类为 HIV 单一感染者的患者,实际上是通过 PCR 分析合并感染的。决策树分析表明,对拉米夫定和恩曲他滨的敏感性是表征合并感染患者的重要特征。总之,本研究首次表明,HIV RT 和 PR 基因的变异性可能是合并感染的遗传生物标志物。