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内源性逆转录分析揭示了携带M184V突变的1型人类免疫缺陷病毒对（-）2'-脱氧-3'-硫代胞苷三磷酸具有高水平抗性。

Endogenous reverse transcription assays reveal high-level resistance to the triphosphate of (-)2'-dideoxy-3'-thiacytidine by mutated M184V human immunodeficiency virus type 1.

作者信息

Quan Y, Gu Z, Li X, Li Z, Morrow C D, Wainberg M A

机构信息

McGill University AIDS Centre, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada.

出版信息

J Virol. 1996 Aug;70(8):5642-5. doi: 10.1128/JVI.70.8.5642-5645.1996.

DOI:10.1128/JVI.70.8.5642-5645.1996
PMID:8764080
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC190526/
Abstract

Kinetic analysis showed that the Ki values and the Ki/Km ratios for mutated, recombinant M184V human immunodeficiency virus type 1 reverse transcriptase (RT) for (-)2'-dideoxy-3'-thiacytidine triphosphate (3TCTP) were 35-fold higher than the equivalent values for wild-type RT but only about twice as high as the equivalent values for each of the triphosphates of ddC (ddCTP) and ddA (ddATP). Fully endogenous RT assays showed that viruses containing the M184V substitution were highly resistant to 3TCTP, with an increase in the 50% inhibitory concentration of 250-fold in comparison with wild-type recombinant virus.

摘要

动力学分析表明，突变的重组M184V 1型人类免疫缺陷病毒逆转录酶（RT）对（-）2'-脱氧-3'-硫代胞苷三磷酸（3TCTP）的Ki值和Ki/Km比是野生型RT相应值的35倍，但仅约为ddC（ddCTP）和ddA（ddATP）各自三磷酸的相应值的两倍。完全内源性RT测定表明，含有M184V替代的病毒对3TCTP具有高度抗性，与野生型重组病毒相比，50%抑制浓度增加了250倍。

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Endogenous reverse transcription assays reveal high-level resistance to the triphosphate of (-)2'-dideoxy-3'-thiacytidine by mutated M184V human immunodeficiency virus type 1.内源性逆转录分析揭示了携带M184V突变的1型人类免疫缺陷病毒对（-）2'-脱氧-3'-硫代胞苷三磷酸具有高水平抗性。
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本文引用的文献

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The same mutation that encodes low-level human immunodeficiency virus type 1 resistance to 2',3'-dideoxyinosine and 2',3'-dideoxycytidine confers high-level resistance to the (-) enantiomer of 2',3'-dideoxy-3'-thiacytidine.编码对2',3'-双脱氧肌苷和2',3'-双脱氧胞苷低水平1型人类免疫缺陷病毒耐药性的相同突变，赋予对2',3'-双脱氧-3'-硫代胞苷(-)对映体的高水平耐药性。
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Mutated K65R recombinant reverse transcriptase of human immunodeficiency virus type 1 shows diminished chain termination in the presence of 2',3'-dideoxycytidine 5'-triphosphate and other drugs.1型人类免疫缺陷病毒的突变型K65R重组逆转录酶在存在2',3'-二脱氧胞苷5'-三磷酸及其他药物的情况下，链终止作用减弱。
Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2760-4. doi: 10.1073/pnas.92.7.2760.
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Inhibition of human immunodeficiency virus type 1 reverse transcriptase by the 5'-triphosphate beta enantiomers of cytidine analogs.胞苷类似物的5'-三磷酸β对映体对人类免疫缺陷病毒1型逆转录酶的抑制作用。
Antimicrob Agents Chemother. 1994 Oct;38(10):2300-5. doi: 10.1128/AAC.38.10.2300.
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The K65R mutant reverse transcriptase of HIV-1 cross-resistant to 2', 3'-dideoxycytidine, 2',3'-dideoxy-3'-thiacytidine, and 2',3'-dideoxyinosine shows reduced sensitivity to specific dideoxynucleoside triphosphate inhibitors in vitro.对2'，3'-二脱氧胞苷、2'，3'-二脱氧-3'-硫代胞苷和2'，3'-二脱氧肌苷具有交叉抗性的HIV-1 K65R突变逆转录酶在体外对特定的双脱氧核苷三磷酸抑制剂的敏感性降低。
J Biol Chem. 1994 Nov 11;269(45):28118-22.
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Development of a human immunodeficiency virus-1 in vitro DNA synthesis system to study reverse transcriptase inhibitors.
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Comparison of deoxyoligonucleotide and tRNA(Lys-3) as primers in an endogenous human immunodeficiency virus-1 in vitro reverse transcription/template-switching reaction.脱氧寡核苷酸与tRNA（Lys-3）作为引物在内源性人类免疫缺陷病毒-1体外逆转录/模板转换反应中的比较。
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