Sensitive phenotypic detection of minor drug-resistant human immunodeficiency virus type 1 reverse transcriptase variants.

Sensitive phenotypic detection of minor drug-resistant human immunodeficiency virus type 1 reverse transcriptase variants.
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轻微耐药人类免疫缺陷病毒 1 型逆转录酶变体的灵敏表型检测。

DOI:
10.1128/jcm.43.11.5696-5704.2005
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发表时间:
2005
影响因子:
9.4
通讯作者:
Strathern,JeffreyN
Strathern,JeffreyN
中科院分区:
医学2区
文献类型:
--
作者:
Nissley,DwightV;Halvas,EliasK;Hoppman,NicoleL;Garfinkel,DavidJ;Mellors,JohnW;Strathern,JeffreyN

文献摘要

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耐药变异的检测对于人类免疫缺陷病毒1型(HIV-1)感染的临床管理和耐药性演变的研究非常重要。在这里,我们表明,由酵母菌反转录转座子Ty 1和HIV-1的逆转录酶(RT)组成的杂交元件是检测,监测和分离耐药逆转录酶的有用工具。这种敏感的表型检测能够检测非核苷逆转录酶的逆转录酶的耐药RT域来自混合物的感染性分子克隆的HIV-1的血浆和临床样本时,变种包括少至0.3%至1%的病毒种群。我们的检测方法可以表征已知和新型逆转录酶变体的活性和药物敏感性,并应证明可用于研究轻微耐药病毒变体的演变和临床意义。
Detection of drug-resistant variants is important for the clinical management of human immunodeficiency virus type 1 (HIV-1) infection and for studies on the evolution of drug resistance. Here we show that hybrid elements composed of theSaccharomyces cerevisiaeretrotransposon Ty1 and the reverse transcriptase (RT) of HIV-1 are useful tools for detecting, monitoring, and isolating drug-resistant reverse transcriptases. This sensitive phenotypic assay is able to detect nonnucleoside reverse transcriptase inhibitor-resistant RT domains derived from mixtures of infectious molecular clones of HIV-1 in plasma and from clinical samples when the variants comprise as little as 0.3 to 1% of the virus population. Our assay can characterize the activities and drug susceptibilities of both known and novel reverse transcriptase variants and should prove useful in studies of the evolution and clinical significance of minor drug-resistant viral variants.