Reverse transcriptase backbone can alter the polymerization and RNase activities of non-nucleoside reverse transcriptase mutants K101E+G190S.
Reverse transcriptase backbone can alter the polymerization and RNase activities of non-nucleoside reverse transcriptase mutants K101E+G190S.
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逆转录酶骨架可以改变非核苷逆转录酶突变体 K101E G190S 的聚合和 RNase 活性。
DOI：
10.1099/vir.0.054999-0
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Dykes,Carrie
中科院分区：
文献类型：
--
作者：
Wang,Jiong;Li,Dongge;Bambara,RobertA;Dykes,Carrie
本课题组前期研究表明，含有非核苷类逆转录酶抑制剂（NNRTI）耐药突变的人类免疫缺陷病毒1型（HIV-1）逆转录酶（RT）存在RNase H活性缺陷以及病毒粒子中RT蛋白数量减少。这些缺陷与缺乏nnrti时的复制适应性有关。K101E+G190S突变组合病毒在NNRTIs存在下比在没有药物的情况下复制得更好。NNRTIs对病毒生长的刺激发生在病毒生命周期的早期阶段，并受到RT主干序列的调节，从而产生抗性突变。我们想要确定在没有NNRTIs的情况下，RT主干序列对RT含量、聚合和RNase H活性的影响。我们将含有K101E+G190S的NL4-3 RT与含有K101E+G190S的患者分离RT序列D10进行了比较。我们在这里发现，与NL4-3主干不同，与WT相比，D10主干序列降低了纯化重组RT的rna依赖的DNA聚合活性。相反，与WT和NL4-3主干中的K101E+G190S相比，D10主干序列的RT具有更高的RNase H活性。与NL4-3骨干中的K101E+G190S相比，D10病毒粒子的RT量也有所增加。我们得出结论，RT的主干序列可以改变NNRTI耐药突变体K101E+G190S的活性，鉴定相关氨基酸将有助于理解NNRTI耐药突变体改变适应度和NNRTIs刺激HIV-1病毒复制的机制。
Previous work by our group showed that human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) containing non-nucleoside RT inhibitor (NNRTI) drug resistance mutations has defects in RNase H activity as well as reduced amounts of RT protein in virions. These deficits correlate with replication fitness in the absence of NNRTIs. Viruses with the mutant combination K101E+G190S replicated better in the presence of NNRTIs than in the absence of drug. Stimulation of virus growth by NNRTIs occurred during the early steps of the virus life cycle and was modulated by the RT backbone sequence in which the resistance mutations arose. We wanted to determine what effects RT backbone sequence would have on RT content and polymerization and RNase H activities in the absence of NNRTIs. We compared a NL4-3 RT with K101E+G190S to a patient-isolate RT sequence D10 with K101E+G190S. We show here that, unlike the NL4-3 backbone, the D10 backbone sequence decreased the RNA-dependent DNA polymerization activity of purified recombinant RT compared to WT. In contrast, RTs with the D10 backbone had increased RNase H activity compared to WT and K101E+G190S in the NL4-3 backbone. D10 virions also had increased amounts of RT compared to K101E+G190S in the NL4-3 backbone. We conclude that the backbone sequence of RT can alter the activities of the NNRTI drug-resistant mutant K101E+G190S, and that identification of the amino acids responsible will aid in understanding the mechanism by which NNRTI drug-resistant mutants alter fitness and NNRTIs stimulate HIV-1 virus replication.
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影响因子：
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作者：
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DOI：
10.1016/j.jcv.2006.01.012
发表时间：
2006
期刊：
Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology
影响因子：
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作者：
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影响因子：
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DOI：
10.1038/nsb0495-303
发表时间：
1995-04-01
期刊：
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影响因子：
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通讯作者：
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DOI：
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发表时间：
1993-07-01
影响因子：
11.1
作者：
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通讯作者：
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