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1型人类免疫缺陷病毒(HIV-1)肯尼亚分离株的基因多样性及自然发生的多态性:对整合酶抑制剂的影响

HIV Type 1 genetic diversity and naturally occurring polymorphisms in HIV type 1 Kenyan isolates: implications for integrase inhibitors.

作者信息

Nyamache Anthony Kebira, Muigai Anne W T, Nganga Zipporah, Khamadi Samoel A

机构信息

Department of Plant and Microbial Sciences, Kenyatta University, Nairobi, Kenya.

出版信息

AIDS Res Hum Retroviruses. 2012 Aug;28(8):933-6. doi: 10.1089/aid.2011.0122. Epub 2011 Dec 16.

Abstract

Little is known about the extent and predictors of polymorphisms potentially influencing susceptibility to HIV integrase inhibitors. HIV-1 genetic diversity and drug resistance are major challenges in patient management globally. To evaluate HIV genetic diversity and drug resistance-associated mutations within a Nairobi cohort, genetic analysis of the HIV-1 pol-integrase gene regions was performed on samples collected from 42 subjects and 113 Kenyan intergrase sequences deposited in the Los Alamos HIV database. From the partial pol-integrase sequences analyzed phylogenetically, it was shown that 26 (61.9%) were subtype A1, 9 (21.4%) were subtype D, 5 (11.9%) were subtype C, 1 (2.4%) was subtype A2 and 1 (2.4%) was subtype CRF. Integrase-associated mutations were found in 12 patients, and in all 113 sequences already deposited in GenBank. One sample from this study and five from previous Kenyan integrase sequences had mutations at T97A, which is associated with reduced susceptibility to raltegravir.

摘要

关于可能影响对HIV整合酶抑制剂易感性的多态性的程度和预测因素,人们了解甚少。HIV-1基因多样性和耐药性是全球患者管理中的主要挑战。为了评估内罗毕一个队列中的HIV基因多样性和与耐药性相关的突变,对从42名受试者采集的样本以及保存在洛斯阿拉莫斯HIV数据库中的113条肯尼亚整合酶序列进行了HIV-1 pol-整合酶基因区域的遗传分析。从系统发育分析的部分pol-整合酶序列来看,结果显示26条(61.9%)为A1亚型,9条(21.4%)为D亚型,5条(11.9%)为C亚型,1条(2.4%)为A2亚型,1条(2.4%)为CRF亚型。在12名患者以及已存入GenBank的所有113条序列中均发现了整合酶相关突变。本研究的一个样本以及之前肯尼亚整合酶序列中的五个样本在T97A处有突变,这与对拉替拉韦的敏感性降低有关。

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