ANALYSIS OF HIV-2 RT MUTANTS PROVIDES EVIDENCE THAT RESISTANCE OF HIV-1 RT AND HIV-2 RT TO NUCLEOSIDE ANALOGS INVOLVES A REPOSITIONING OF THE TEMPLATE-PRIMER

Perach M.; Hughes SH.; Hizi A.; Rubinek T.

首页> 外文期刊>Journal of Molecular Biology >ANALYSIS OF HIV-2 RT MUTANTS PROVIDES EVIDENCE THAT RESISTANCE OF HIV-1 RT AND HIV-2 RT TO NUCLEOSIDE ANALOGS INVOLVES A REPOSITIONING OF THE TEMPLATE-PRIMER

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ANALYSIS OF HIV-2 RT MUTANTS PROVIDES EVIDENCE THAT RESISTANCE OF HIV-1 RT AND HIV-2 RT TO NUCLEOSIDE ANALOGS INVOLVES A REPOSITIONING OF THE TEMPLATE-PRIMER

机译：对HIV-2 RT突变体的分析提供的证据表明，HIV-1 RT和HIV-2 RT对核苷类似物的耐药性涉及模板聚合物的重新定位

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Mutations that confer resistance to nucleoside analogs do not cluster around the deoxynucleotide triphosphate (dNTP) binding site. Instead, these mutations appear to lie along the groove in the enzyme where the template-primer binds. Based on such structural data and on complementary biochemical analyses, it has been suggested that resistance to nucleoside analogs involves repositioning of the template-primer. We have prepared mutations in HIV-2 RT that are the homologs of mutations that confer resistance to nucleoside analogs in HIV-1 RT. Analysis of the behavior of HIV-2 RT mutants (Leu74Val, Glu89Gly, Ser215Tyr, Leu74-Val/Ser215Tyr and Glu89Gly/Ser215Tyr) in vitro confirms the results obtained with HIV-1 RT: resistance is a function of the length of the template overhang. These analyses also suggest that the homolog in HIV-2 RT of one of the mutations that confers resistance to AZT in HIV-1 RT (Thr215Tyr) confers resistance by repositioning of the template-primer. [References: 31]

机译：赋予对核苷类似物抗性的突变不会聚集在脱氧核苷酸三磷酸（dNTP）结合位点周围。相反，这些突变似乎是沿着模板引物结合的酶的凹槽。基于这样的结构数据和互补的生化分析，已经表明对核苷类似物的抗性涉及模板引物的重新定位。我们已经准备了HIV-2 RT中的突变，这些突变是赋予HIV-1 RT中核苷类似物抗性的突变的同源物。体外对HIV-2 RT突变体（Leu74Val，Glu89Gly，Ser215Tyr，Leu74-Val / Ser215Tyr和Glu89Gly / Ser215Tyr）行为的分析证实了HIV-1 RT的结果：抗性是模板突出端长度的函数。这些分析还表明，在HIV-2 RT中，赋予HIV-1 RT（Thr215Tyr）AZT抗性的突变之一的同源物通过重新定位模板引物而赋予抗性。 [参考：31]

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《Journal of Molecular Biology》 |1997年第3期|共7页
作者
Perach M.; Hughes SH.; Hizi A.; Rubinek T.;
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正文语种 eng
中图分类分子生物学;
关键词
Transcriptase; Hiv-1; Hiv-2; Drug-resistance; Nucleoside analogs; Immunodeficiency-virus type-1; Murine leukemia-virus; Reverse-transcriptase; Nonnucleoside inhibitors; Angstrom resolution; Crystal-structure; Mutations; Aids; Sensitivity; Mechanisms;

机译：转录酶;Hiv-1;Hiv-2;耐药性;核苷类似物;免疫缺陷病毒1型;鼠白血病病毒;逆转录酶;非核苷抑制剂;埃分辨力;晶体结构;突变;助剂;敏感性;机制;

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1. ANALYSIS OF HIV-2 RT MUTANTS PROVIDES EVIDENCE THAT RESISTANCE OF HIV-1 RT AND HIV-2 RT TO NUCLEOSIDE ANALOGS INVOLVES A REPOSITIONING OF THE TEMPLATE-PRIMER [J] . Perach M., Hughes SH., Hizi A., Journal of Molecular Biology . 1997,第3期

机译：对HIV-2 RT突变体的分析提供的证据表明，HIV-1 RT和HIV-2 RT对核苷类似物的耐药性涉及模板聚合物的重新定位
2. Comparison of the Antiviral Activity of Bictegravir against HIV-1 and HIV-2 Isolates and Integrase Inhibitor-Resistant HIV-2 Mutants [J] . Smith Robert A., Raugi Dana N., Wu Vincent H., Antimicrobial agents and chemotherapy. . 2019,第5期

机译：Bictegravir对HIV-1和HIV-2分离株和整合酶抑制的HIV-2突变体的抗病毒活性的比较
3. A Single-tube real-time RT-PCR assay for RNA detection and quantification of genetically diverse HIV including rare HIV-1 non-m groups and HIV-2 [J] . Prasolova M. A., Ivanov M. K., Gashnikova N. M., Molecular Genetics , Microbiology and Virology: Molekulyarnaya Genetika , Mikrobiologiya i Virusologiya . 2014,第4期

机译：单管实时RT-PCR测定法，用于RNA检测和定量分析遗传多样的HIV，包括罕见的HIV-1非m组和HIV-2
4. Analysis and Comparison of Genomes of HIV-1 and HIV-2 Using Apriori Algorithm, Decision Tree, and Support Vector Machine [C] . Yihyun Roh, Seokhyun Yoon, Min Young Lee, International conference on advanced intelligent computing theories and applications . 2016

机译：利用Apriori算法，决策树和支持向量机对HIV-1和HIV-2基因组进行分析和比较
5. Part I: Synthesis of Cyclobutyl Nucleoside Analogs That Mimic AZT for Inhibition of the K65R HIV-1 Reverse Transcriptase Mutant. Part II: Synthesis and Evaluation of Truncated Triptolide Analogs to Suppress Chronic Inflammation [D] . Bluemling, Gregory Richard 2011

机译：第一部分：模拟AZT抑制K65R HIV-1逆转录酶突变体的环丁基核苷类似物的合成。第二部分：截短雷公藤甲素类似物的合成和评估，以抑制慢性炎症
6. Selective pressure of a quinoxaline nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) on HIV-1 replication results in the emergence of nucleoside RT-inhibitor-specific (RT Leu-74--Val or Ile and Val-75--Leu or Ile) HIV-1 mutants. [O] . J P Kleim, M Rösner, I Winkler, 1996

机译：喹喔啉非1型人类免疫缺陷病毒（HIV-1）逆转录酶（RT）抑制剂对HIV-1复制的选择性压力导致出现核苷RT抑制剂特异性（RT Leu-74- Val或Ile和Val-75- Leu或Ile）HIV-1突变体。
7. Selective pressure of a quinoxaline nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) on HIV-1 replication results in the emergence of nucleoside RT-inhibitor-specific (RT Leu-74-->Val or Ile and Val-75-->Leu or Ile) HIV-1 mutants. [O] . Kleim, J P, Rösner, M, Winkler, I, 1996

机译：1型人类免疫缺陷病毒（HIV-1）逆转录酶（RT）喹喔啉非核苷抑制剂对HIV-1复制的选择性压力导致出现核苷RT抑制剂特异性（RT Leu-74-> Val或Ile和Val-75-> Leu或Ile）HIV-1突变体。

ANALYSIS OF HIV-2 RT MUTANTS PROVIDES EVIDENCE THAT RESISTANCE OF HIV-1 RT AND HIV-2 RT TO NUCLEOSIDE ANALOGS INVOLVES A REPOSITIONING OF THE TEMPLATE-PRIMER

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