The HIV-1 reverse transcriptase mutants G190S and G190A, which confer resistance to non-nucleoside reverse transcriptase inhibitors, demonstrate reductions in RNase H activity and DNA synthesis from tRNA(Lys,3) that correlate with reductions in replication efficiency

Wang J.; Dykes C.; Domaoal R. A.; Koval C. E.; Bambara R. A.; Demeter L. M.

首页> 外文期刊>Virology >The HIV-1 reverse transcriptase mutants G190S and G190A, which confer resistance to non-nucleoside reverse transcriptase inhibitors, demonstrate reductions in RNase H activity and DNA synthesis from tRNA(Lys,3) that correlate with reductions in replication efficiency

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The HIV-1 reverse transcriptase mutants G190S and G190A, which confer resistance to non-nucleoside reverse transcriptase inhibitors, demonstrate reductions in RNase H activity and DNA synthesis from tRNA(Lys,3) that correlate with reductions in replication efficiency

机译：HIV-1逆转录酶突变体G190S和G190A赋予了非核苷逆转录酶抑制剂的抗性，证明RNase H活性的降低和tRNA（Lys，3）的DNA合成与复制效率的降低相关

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We evaluated the replication efficiency of the HIV reverse transcriptase (RT) mutants K103N, G190A, and G190S, which confer resistance to the non-nucleoside RT inhibitor efavirenz, using growth competition assays in cell culture. In the absence of efavirenz, the fitness hierarchy was G190S & G190A & K103N & wild-type. The fitness reduction of G190S relative to K103N was less evident at high efavirenz concentrations, although K103N still replicated more efficiently. Efficiency of RNase H cleavage and RNA-dependent DNA synthesis from tRNA(Lys,3) Correlated with relative fitness, in biochemical studies of mutant RTs. Presteady state and steady state polymerization assays using DNA primers detected no abnormalities. This work is consistent with previous studies demonstrating that initiation of viral DNA synthesis is reduced in mutants with slowed RNase H cleavage, and suggests that both abnormalities contribute to the replication defect of these mutants. It also suggests that high concentrations of efavirenz are unlikely to favor the selection of G190S clinically. (c) 2006 Elsevier Inc. All rights reserved.

机译：我们使用细胞培养中的生长竞争测定法评估了HIV逆转录酶（RT）突变体K103N，G190A和G190S的复制效率，这些突变体赋予了对非核苷RT抑制剂依非韦伦的耐药性。在没有依法韦仑的情况下，适应度等级为G190S ＜1。 G190A ＜ K103N ＜野生型。在高依非韦伦浓度下，G190S相对于K103N的适应性降低不太明显，尽管K103N仍能更有效地复制。在突变体RTs的生化研究中，tRNA（Lys，3）的RNase H裂解效率和RNA依赖性DNA合成的效率与相对适应性相关。使用DNA引物进行的稳态和稳态聚合测定均未发现异常。这项工作与先前的研究一致，该研究表明在具有缓慢的RNase H切割的突变体中病毒DNA合成的起始减少了，并且表明这两种异常均导致了这些突变体的复制缺陷。这也表明高浓度的依非韦伦不太可能在临床上有利于G190S的选择。（c）2006 Elsevier Inc.保留所有权利。

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《Virology》 |2006年第2期|共13页
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Wang J.; Dykes C.; Domaoal R. A.; Koval C. E.; Bambara R. A.; Demeter L. M.;
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正文语种 eng
中图分类人体病毒学（致病病毒）;医学微生物学（病原细菌学、病原微生物学）;人体病毒学（致病病毒）;
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drug resistance;

机译：耐药性;

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1. The HIV-1 reverse transcriptase mutants G190S and G190A, which confer resistance to non-nucleoside reverse transcriptase inhibitors, demonstrate reductions in RNase H activity and DNA synthesis from tRNA(Lys,3) that correlate with reductions in replication efficiency [J] . Wang J., Dykes C., Domaoal R. A., Virology . 2006,第2期

机译：HIV-1逆转录酶突变体G190S和G190A赋予了非核苷逆转录酶抑制剂的抗性，证明RNase H活性的降低和tRNA（Lys，3）的DNA合成与复制效率的降低相关
2. Alizarine derivatives as new dual inhibitors of the HIV-1 reverse transcriptase-associated DNA polymerase and RNase H activities effective also on the RNase H activity of non-nucleoside resistant reverse transcriptases [J] . Esposito Francesca, Kharlamova Tatyana, Distinto Simona, The FEBS journal . 2011,第9期

机译：茜素衍生物作为HIV-1逆转录酶相关DNA聚合酶和RNase H活性的新型双重抑制剂，对非核苷抗性逆转录酶的RNase H活性也有效
3. Initiation of (-) strand DNA synthesis from tRNA_3~Lys on lentiviral RNAs: Implications of specific HIV-1 RNA-tRNA_3~Lys interactions inhibiting primer utilization by retroviral reverse transcriptases [J] . Eric J. Arts, Scott R. Stetor, Xuguang Li Proceedings of the National Academy of Sciences of the United States of America . 1996,第19期

机译：从慢病毒RNA上的tRNA_3〜Lys（-）链DNA合成的启动：特定HIV-1 RNA-tRNA_3〜Lys相互作用的影响抑制了逆转录病毒逆转录酶对引物的利用
4. A Novel Detection of Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs) for HIV-1 with AlGaN/GaN High Electron Mobility Transistors [C] . Yen-Wen Kang, Geng-Yen Lee, Jen-Inn Chyi, Symposium on wide bandgap semiconductor materials and devices;Meeting of the Electrochemical Society . 2013

机译：AlGaN / GaN高电子迁移率晶体管对HIV-1的非核苷逆转录酶抑制剂（NNRTIs）的新型检测
5. Biochemical characterization of human immunodeficiency virus type 1 reverse transcriptase mutants to non-nucleoside reverse transcriptase inhibitors [D] . Domaoal, Robert A. 2005

机译：人类免疫缺陷病毒1型逆转录酶突变体对非核苷类逆转录酶抑制剂的生化特性
6. The HIV-1 reverse transcriptase mutants G190S and G190A which confer resistance to non-nucleoside reverse transcriptase inhibitors demonstrate reductions in RNase H activity and DNA synthesis from tRNALys3 that correlate with reductions in replication efficiency [O] . J. Wang, C. Dykes, R.A. Domaoal, -1

机译：HIV-1逆转录酶突变体G190S和G190A赋予了非核苷逆转录酶抑制剂的抗性证明RNase H活性降低和tRNALys合成DNA的减少3与复制效率的降低相关
7. The HIV-1 reverse transcriptase mutants G190S and G190A, which confer resistance to non-nucleoside reverse transcriptase inhibitors, demonstrate reductions in RNase H activity and DNA synthesis from tRNALys, 3 that correlate with reductions in replication efficiency [O] . J. Wang, C. Dykes, R.A. Domaoal, 2006

机译：HIV-1逆转录酶突变体G190S和G190A，其赋予非核苷逆转录酶抑制剂的抗性，证明了RNA酶H活性和从TRNARY的DNA合成的降低，3与复制效率的降低相关

The HIV-1 reverse transcriptase mutants G190S and G190A, which confer resistance to non-nucleoside reverse transcriptase inhibitors, demonstrate reductions in RNase H activity and DNA synthesis from tRNA(Lys,3) that correlate with reductions in replication efficiency

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