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1
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.
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
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.
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Rapid phenotypic reversion of zidovudine-resistant feline immunodeficiency virus without loss of drug-resistant reverse transcriptase.齐多夫定耐药型猫免疫缺陷病毒的快速表型逆转，且耐药性逆转录酶未丢失
J Virol. 1994 Feb;68(2):632-7. doi: 10.1128/JVI.68.2.632-637.1994.
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
Selection and characterization of a mutant of feline immunodeficiency virus resistant to 2',3'-dideoxycytidine.对2'，3'-双脱氧胞苷具有抗性的猫免疫缺陷病毒突变体的筛选与鉴定
Antimicrob Agents Chemother. 1996 Apr;40(4):953-7. doi: 10.1128/AAC.40.4.953.
7
Mutants of feline immunodeficiency virus resistant to 3'-azido-3'-deoxythymidine.对3'-叠氮-3'-脱氧胸苷耐药的猫免疫缺陷病毒突变体。
J Virol. 1991 Jan;65(1):308-12. doi: 10.1128/JVI.65.1.308-312.1991.
8
Mutants of feline immunodeficiency virus resistant to 2',3'-dideoxy-2',3'-didehydrothymidine.对2'，3'-双脱氧-2'，3'-双脱氢胸苷具有抗性的猫免疫缺陷病毒突变体。
Antimicrob Agents Chemother. 1996 Sep;40(9):1983-7. doi: 10.1128/AAC.40.9.1983.
9
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.
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A novel polymorphism at codon 333 of human immunodeficiency virus type 1 reverse transcriptase can facilitate dual resistance to zidovudine and L-2',3'-dideoxy-3'-thiacytidine.人类免疫缺陷病毒1型逆转录酶第333位密码子处的一种新型多态性可促成对齐多夫定和L-2'，3'-二脱氧-3'-硫代胞苷的双重耐药性。
J Virol. 1998 Jun;72(6):5093-8. doi: 10.1128/JVI.72.6.5093-5098.1998.

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Viruses. 2023 Mar 24;15(4):822. doi: 10.3390/v15040822.
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Viruses. 2018 Apr 20;10(4):206. doi: 10.3390/v10040206.
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Efficacy of Antiviral Drugs against Feline Immunodeficiency Virus.抗病毒药物对猫免疫缺陷病毒的疗效
Vet Sci. 2015 Dec 18;2(4):456-476. doi: 10.3390/vetsci2040456.
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J Feline Med Surg. 2015 Nov;17(11):925-39. doi: 10.1177/1098612X15610676.
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Follow-up on long-term antiretroviral therapy for cats infected with feline immunodeficiency virus.感染猫免疫缺陷病毒的猫长期抗逆转录病毒治疗的随访
J Feline Med Surg. 2016 Apr;18(4):264-72. doi: 10.1177/1098612X15580144. Epub 2015 Apr 8.
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Phylogenetic and genetic analysis of feline immunodeficiency virus gag, pol, and env genes from domestic cats undergoing nucleoside reverse transcriptase inhibitor treatment or treatment-naïve cats in Rio de Janeiro, Brazil.对巴西里约热内卢接受核苷类逆转录酶抑制剂治疗的家猫或未接受过治疗的家猫的猫免疫缺陷病毒gag、pol和env基因进行系统发育和遗传分析。
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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。
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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。
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本文引用的文献

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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。
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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.
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Mutants of feline immunodeficiency virus resistant to 2',3'-dideoxy-2',3'-didehydrothymidine.对2'，3'-双脱氧-2'，3'-双脱氢胸苷具有抗性的猫免疫缺陷病毒突变体。
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Mechanisms of nucleoside analog antiviral activity and resistance during human immunodeficiency virus reverse transcription.人类免疫缺陷病毒逆转录过程中核苷类似物抗病毒活性及耐药性的机制
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Selection and characterization of a mutant of feline immunodeficiency virus resistant to 2',3'-dideoxycytidine.对2'，3'-双脱氧胞苷具有抗性的猫免疫缺陷病毒突变体的筛选与鉴定
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Human immunodeficiency virus type-1 reverse transcriptase. Contribution of Met-184 to binding of nucleoside 5'-triphosphate.人类免疫缺陷病毒1型逆转录酶。甲硫氨酸184对核苷5'-三磷酸结合的作用。
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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。

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.

作者信息

Smith R A, Remington K M, Preston B D, Schinazi R F, North T W

机构信息

Division of Biological Sciences, the University of Montana, Missoula 59812, USA.

出版信息

J Virol. 1998 Mar;72(3):2335-40. doi: 10.1128/JVI.72.3.2335-2340.1998.

DOI:10.1128/JVI.72.3.2335-2340.1998
PMID:9499094
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC109533/
Abstract

Mutants of feline immunodeficiency virus (FIV) resistant to (-)-beta-2',3'-dideoxy-3'-thiacytidine (3TC) were selected by culturing virus in the presence of increasing stepwise concentrations of 3TC. Two plaque-purified variants were isolated from the original mutant population, and both of these mutants were resistant to 3TC. Surprisingly, these mutants were also phenotypically resistant to 3'-azido-3'-deoxythymidine (AZT) and to the combination of 3TC and AZT. Purified reverse transcriptase (RT) from one of these plaque-purified mutants was resistant to the 5'-triphosphates of 3TC and AZT. DNA sequence analysis of the RT-encoding region of the pol gene amplified from the plaque-purified mutants revealed a Pro-to-Ser mutation at position 156 of RT. A site-directed mutant of FIV engineered to contain this Pro-156-Ser mutation was resistant to 3TC, AZT, and the combination of 3TC and AZT, confirming the role of the Pro-156-Ser mutation in the resistance of FIV to these two nucleoside analogs. This represents the first report of a lentiviral mutant resistant to the combination of AZT and 3TC due to a single, unique point mutation.

摘要

通过在逐步增加浓度的（-）-β-2'，3'-二脱氧-3'-硫代胞苷（3TC）存在下培养猫免疫缺陷病毒（FIV），筛选出对3TC耐药的FIV突变体。从原始突变群体中分离出两个经噬斑纯化的变体，这两个突变体均对3TC耐药。令人惊讶的是，这些突变体在表型上也对3'-叠氮-3'-脱氧胸苷（AZT）以及3TC与AZT的组合耐药。从其中一个经噬斑纯化的突变体中纯化得到的逆转录酶（RT）对3TC和AZT的5'-三磷酸酯耐药。对从经噬斑纯化的突变体中扩增的pol基因RT编码区进行DNA序列分析，结果显示RT第156位发生了脯氨酸到丝氨酸的突变。构建的含有该Pro-156-Ser突变的FIV定点突变体对3TC、AZT以及3TC与AZT的组合均耐药，这证实了Pro-156-Ser突变在FIV对这两种核苷类似物耐药中的作用。这是关于慢病毒突变体因单个独特点突变而对AZT和3TC组合耐药的首次报道。