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1
Mutations at codon 184 in simian immunodeficiency virus reverse transcriptase confer resistance to the (-) enantiomer of 2',3'-dideoxy-3'-thiacytidine.猿猴免疫缺陷病毒逆转录酶第184位密码子的突变赋予了对2',3'-二脱氧-3'-硫代胞苷（-）对映体的抗性。
Antimicrob Agents Chemother. 1997 Dec;41(12):2763-5. doi: 10.1128/AAC.41.12.2763.
2
Reversion of the M184V mutation in simian immunodeficiency virus reverse transcriptase is selected by tenofovir, even in the presence of lamivudine.即使在拉米夫定存在的情况下，替诺福韦也能选择出猿猴免疫缺陷病毒逆转录酶中M184V突变的回复突变。
J Virol. 2003 Jan;77(2):1120-30. doi: 10.1128/jvi.77.2.1120-1130.2003.
3
In vitro characterization of FIV-pPPR, a pathogenic molecular clone of feline immunodeficiency virus, and two drug-resistant pol gene mutants.猫免疫缺陷病毒致病分子克隆FIV-pPPR及两种耐药性pol基因突变体的体外特性研究
Am J Vet Res. 2001 Apr;62(4):588-94. doi: 10.2460/ajvr.2001.62.588.
4
Identification of a mutation at codon 65 in the IKKK motif of reverse transcriptase that encodes human immunodeficiency virus resistance to 2',3'-dideoxycytidine and 2',3'-dideoxy-3'-thiacytidine.在编码对2'，3'-双脱氧胞苷和2'，3'-双脱氧-3'-硫代胞苷具有人类免疫缺陷病毒抗性的逆转录酶的IKKK基序中第65密码子处鉴定出一种突变。
Antimicrob Agents Chemother. 1994 Feb;38(2):275-81. doi: 10.1128/AAC.38.2.275.
5
Rapid in vitro selection of human immunodeficiency virus type 1 resistant to 3'-thiacytidine inhibitors due to a mutation in the YMDD region of reverse transcriptase.由于逆转录酶YMDD区域的突变，人免疫缺陷病毒1型对3'-硫代胞苷抑制剂产生快速体外抗性。
Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5653-6. doi: 10.1073/pnas.90.12.5653.
6
Wild-type and YMDD mutant murine leukemia virus reverse transcriptases are resistant to 2',3'-dideoxy-3'-thiacytidine.野生型和YMDD突变型鼠白血病病毒逆转录酶对2'，3'-二脱氧-3'-硫代胞苷具有抗性。
J Virol. 2000 Jul;74(14):6669-74. doi: 10.1128/jvi.74.14.6669-6674.2000.
7
Retention of marked sensitivity to (S)-4-isopropoxycarbonyl-6-methoxy-3-(methylthiomethyl)-3,4-di hydroquin oxaline-2(1H)-thione (HBY 097) by an azidothymidine (AZT)-resistant human immunodeficiency virus type 1 (HIV-1) strain subcultured in the combined presence of quinoxaline HBY 097 and 2',3'-dideoxy-3'-thiacytidine (lamivudine).在喹喔啉HBY 097和2'，3'-二脱氧-3'-硫代胞苷（拉米夫定）联合存在的情况下传代培养的对叠氮胸苷（AZT）耐药的1型人类免疫缺陷病毒（HIV-1）毒株对（S）-4-异丙氧基羰基-6-甲氧基-3-（甲硫基甲基）-3,4-二氢喹喔啉-2（1H）-硫酮（HBY 097）保持显著敏感性。
Biochem Pharmacol. 1998 Mar 1;55(5):617-25. doi: 10.1016/s0006-2952(97)00506-6.
8
A novel point mutation at position 156 of reverse transcriptase from feline immunodeficiency virus confers resistance to the combination of (-)-beta-2',3'-dideoxy-3'-thiacytidine and 3'-azido-3'-deoxythymidine.猫免疫缺陷病毒逆转录酶第156位的一个新型点突变赋予了对（-）-β-2'，3'-二脱氧-3'-硫代胞苷和3'-叠氮基-3'-脱氧胸苷联合用药的抗性。
J Virol. 1998 Mar;72(3):2335-40. doi: 10.1128/JVI.72.3.2335-2340.1998.
9
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。
Antimicrob Agents Chemother. 1993 Jun;37(6):1390-2. doi: 10.1128/AAC.37.6.1390.
10
High-level resistance to (-) enantiomeric 2'-deoxy-3'-thiacytidine in vitro is due to one amino acid substitution in the catalytic site of human immunodeficiency virus type 1 reverse transcriptase.对（-）对映体2'-脱氧-3'-硫代胞苷的高水平体外抗性是由于1型人类免疫缺陷病毒逆转录酶催化位点的一个氨基酸取代。
Antimicrob Agents Chemother. 1993 Oct;37(10):2231-4. doi: 10.1128/AAC.37.10.2231.

引用本文的文献

1
Characterization of the Drug Resistance Profiles of Integrase Strand Transfer Inhibitors in Simian Immunodeficiency Virus SIVmac239.猿猴免疫缺陷病毒SIVmac239中整合酶链转移抑制剂耐药谱的特征分析
J Virol. 2015 Dec;89(23):12002-13. doi: 10.1128/JVI.02131-15. Epub 2015 Sep 16.
2
Reduced dNTP binding affinity of 3TC-resistant M184I HIV-1 reverse transcriptase variants responsible for viral infection failure in macrophage.对巨噬细胞中病毒感染失败负责的3TC耐药M184I HIV-1逆转录酶变体的dNTP结合亲和力降低。
J Biol Chem. 2008 Apr 4;283(14):9206-16. doi: 10.1074/jbc.M710149200. Epub 2008 Jan 24.
3
Molecular impact of the M184V mutation in human immunodeficiency virus type 1 reverse transcriptase.人类免疫缺陷病毒1型逆转录酶中M184V突变的分子影响
Antimicrob Agents Chemother. 2003 Nov;47(11):3377-83. doi: 10.1128/AAC.47.11.3377-3383.2003.
4
Reversion of the M184V mutation in simian immunodeficiency virus reverse transcriptase is selected by tenofovir, even in the presence of lamivudine.即使在拉米夫定存在的情况下，替诺福韦也能选择出猿猴免疫缺陷病毒逆转录酶中M184V突变的回复突变。
J Virol. 2003 Jan;77(2):1120-30. doi: 10.1128/jvi.77.2.1120-1130.2003.
5
The M184V mutation in reverse transcriptase can delay reversion of attenuated variants of simian immunodeficiency virus.逆转录酶中的M184V突变可延缓猿猴免疫缺陷病毒减毒株变体的回复突变。
J Virol. 2002 Sep;76(17):8958-62. doi: 10.1128/jvi.76.17.8958-8962.2002.
6
Virulence and reduced fitness of simian immunodeficiency virus with the M184V mutation in reverse transcriptase.逆转录酶中具有M184V突变的猿猴免疫缺陷病毒的毒力和适应性降低
J Virol. 2002 Jun;76(12):6083-92. doi: 10.1128/jvi.76.12.6083-6092.2002.
7
Wild-type and YMDD mutant murine leukemia virus reverse transcriptases are resistant to 2',3'-dideoxy-3'-thiacytidine.野生型和YMDD突变型鼠白血病病毒逆转录酶对2'，3'-二脱氧-3'-硫代胞苷具有抗性。
J Virol. 2000 Jul;74(14):6669-74. doi: 10.1128/jvi.74.14.6669-6674.2000.
8
Lamivudine (3TC) resistance in HIV-1 reverse transcriptase involves steric hindrance with beta-branched amino acids.HIV-1逆转录酶对拉米夫定（3TC）的耐药性涉及与β-支链氨基酸的空间位阻。
Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10027-32. doi: 10.1073/pnas.96.18.10027.

本文引用的文献

1
Initial appearance of the 184Ile variant in lamivudine-treated patients is caused by the mutational bias of human immunodeficiency virus type 1 reverse transcriptase.在接受拉米夫定治疗的患者中，184Ile变体的初次出现是由1型人类免疫缺陷病毒逆转录酶的突变偏向性引起的。
J Virol. 1997 Apr;71(4):3346-50. doi: 10.1128/JVI.71.4.3346-3350.1997.
2
A novel Met-to-Thr mutation in the YMDD motif of reverse transcriptase from feline immunodeficiency virus confers resistance to oxathiolane nucleosides.猫免疫缺陷病毒逆转录酶的YMDD基序中一种新的甲硫氨酸到苏氨酸突变赋予对氧硫杂环戊烷核苷的抗性。
J Virol. 1997 Mar;71(3):2357-62. doi: 10.1128/JVI.71.3.2357-2362.1997.
3
A zidovudine-resistant simian immunodeficiency virus mutant with a Q151M mutation in reverse transcriptase causes AIDS in newborn macaques.一种在逆转录酶中具有Q151M突变的齐多夫定耐药性猿猴免疫缺陷病毒突变体可导致新生猕猴患艾滋病。
Antimicrob Agents Chemother. 1997 Feb;41(2):278-83. doi: 10.1128/AAC.41.2.278.
4
Reduced replication of 3TC-resistant HIV-1 variants in primary cells due to a processivity defect of the reverse transcriptase enzyme.由于逆转录酶的持续合成能力缺陷，3TC耐药性HIV-1变体在原代细胞中的复制减少。
EMBO J. 1996 Aug 1;15(15):4040-9.
5
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。
Antimicrob Agents Chemother. 1993 Jun;37(6):1390-2. doi: 10.1128/AAC.37.6.1390.
6
Molecular and biological characterization of simian immunodeficiency virus macaque strain 32H proviral clones containing nef size variants.含有nef大小变异体的猿猴免疫缺陷病毒猕猴株32H前病毒克隆的分子和生物学特性
J Gen Virol. 1994 Mar;75 ( Pt 3):529-43. doi: 10.1099/0022-1317-75-3-529.
7
Rapid in vitro selection of human immunodeficiency virus type 1 resistant to 3'-thiacytidine inhibitors due to a mutation in the YMDD region of reverse transcriptase.由于逆转录酶YMDD区域的突变，人免疫缺陷病毒1型对3'-硫代胞苷抑制剂产生快速体外抗性。
Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5653-6. doi: 10.1073/pnas.90.12.5653.
8
Characterization of human immunodeficiency viruses resistant to oxathiolane-cytosine nucleosides.对奥沙硫杂环戊烷胞嘧啶核苷耐药的人类免疫缺陷病毒的特性分析
Antimicrob Agents Chemother. 1993 Apr;37(4):875-81. doi: 10.1128/AAC.37.4.875.
9
Potential mechanism for sustained antiretroviral efficacy of AZT-3TC combination therapy.齐多夫定-拉米夫定联合疗法持续抗逆转录病毒疗效的潜在机制。
Science. 1995 Aug 4;269(5224):696-9. doi: 10.1126/science.7542804.
10
Sensitivity/resistance profile of a simian immunodeficiency virus containing the reverse transcriptase gene of human immunodeficiency virus type 1 (HIV-1) toward the HIV-1-specific non-nucleoside reverse transcriptase inhibitors.一种含有1型人类免疫缺陷病毒（HIV-1）逆转录酶基因的猿猴免疫缺陷病毒对HIV-1特异性非核苷类逆转录酶抑制剂的敏感性/耐药性概况。
Biochem Biophys Res Commun. 1995 Jun 26;211(3):850-6. doi: 10.1006/bbrc.1995.1890.

猿猴免疫缺陷病毒逆转录酶第184位密码子的突变赋予了对2',3'-二脱氧-3'-硫代胞苷（-）对映体的抗性。

Mutations at codon 184 in simian immunodeficiency virus reverse transcriptase confer resistance to the (-) enantiomer of 2',3'-dideoxy-3'-thiacytidine.

作者信息

Cherry E, Slater M, Salomon H, Rud E, Wainberg M A

机构信息

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

出版信息

Antimicrob Agents Chemother. 1997 Dec;41(12):2763-5. doi: 10.1128/AAC.41.12.2763.

DOI:10.1128/AAC.41.12.2763
PMID:9420055
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC164205/
Abstract

Variants of simian immunodeficiency virus (SIV) that display greater than 2,000-fold resistance to the (-) enantiomer of 2',3'-dideoxy-3'-thiacytidine (3TC) were generated through in vitro passage and drug selection. The polymerase regions of several of these resistant viruses were sequenced and were found to share either of two codon alterations at site 184 in reverse transcriptase (ATG to ATA [methionine to isoleucine] and ATG to GTA [methionine to valine]). The biological relevance of these substitutions for 3TC was confirmed by site-directed mutagenesis with the SIVmac239 infectious recombinant clone of SIV.

摘要

通过体外传代和药物筛选，产生了对2'，3'-二脱氧-3'-硫代胞苷（3TC）的（-）对映体具有超过2000倍抗性的猿猴免疫缺陷病毒（SIV）变体。对其中几种抗性病毒的聚合酶区域进行了测序，发现它们在逆转录酶的第184位共享两种密码子改变之一（ATG变为ATA [甲硫氨酸变为异亮氨酸]和ATG变为GTA [甲硫氨酸变为缬氨酸]）。通过使用SIV的SIVmac239感染性重组克隆进行定点诱变，证实了这些取代对3TC的生物学相关性。