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一名艾滋病患者连续分离出的HIV-1毒株中的逆转录酶突变

Reverse transcriptase mutations in sequential HIV-1 isolates in a patient with AIDS.

作者信息

Gurusinghe A D, Land S A, Birch C, McGavin C, Hooker D J, Tachedjian G, Doherty R, Deacon N J

机构信息

AIDS Molecular Biology Laboratory, Macfarlane Burnet Centre for Medical Research, Fairfield, Victoria, Australia.

出版信息

J Med Virol. 1995 Jul;46(3):238-43. doi: 10.1002/jmv.1890460312.

DOI:10.1002/jmv.1890460312
PMID:7561796
Abstract

Sequential human immunodeficiency virus type 1 (HIV-1) isolates were obtained over a 29-month period from a person before, during, and after AZT therapy. DNA sequence analysis of polymerase chain-amplified reverse-transcriptase gene showed a gradual accumulation of mutations to peak resistance (IC50 2.13 microM AZT) in association with mutations at codons 44, 210, and 369, as well as at 41, 67, 70, and 215. Eight months after cessation of AZT therapy, when an HIV-1 isolate from the patient was again sensitive to AZT, these mutations had all returned to the pretherapy sequence.

摘要

在29个月的时间里,从一名接受齐多夫定(AZT)治疗前、治疗期间及治疗后的患者身上获取了一系列1型人类免疫缺陷病毒(HIV-1)分离株。对聚合酶链反应扩增的逆转录酶基因进行DNA序列分析显示,与第44、210和369位密码子以及第41、67、70和215位密码子的突变相关,突变逐渐积累至耐药峰值(IC50为2.13 microM AZT)。在停止AZT治疗8个月后,当从该患者身上分离的HIV-1毒株再次对AZT敏感时,这些突变均恢复到治疗前的序列。

相似文献

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Reverse transcriptase mutations in sequential HIV-1 isolates in a patient with AIDS.一名艾滋病患者连续分离出的HIV-1毒株中的逆转录酶突变
J Med Virol. 1995 Jul;46(3):238-43. doi: 10.1002/jmv.1890460312.
2
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Reverse transcriptase sequence of paired isolates of cerebrospinal fluid and blood from patients infected with human immunodeficiency virus type 1 during zidovudine treatment.齐多夫定治疗期间感染1型人类免疫缺陷病毒的患者脑脊液和血液配对分离株的逆转录酶序列
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pol mutations conferring zidovudine and didanosine resistance with different effects in vitro yield multiply resistant human immunodeficiency virus type 1 isolates in vivo.赋予齐多夫定和去羟肌苷耐药性且在体外具有不同效应的pol突变,在体内产生多重耐药的1型人类免疫缺陷病毒分离株。
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Multiple mutations in HIV-1 reverse transcriptase confer high-level resistance to zidovudine (AZT).HIV-1逆转录酶中的多个突变赋予对齐多夫定(AZT)的高水平耐药性。
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An in vivo mutation from leucine to tryptophan at position 210 in human immunodeficiency virus type 1 reverse transcriptase contributes to high-level resistance to 3'-azido-3'-deoxythymidine.人类免疫缺陷病毒1型逆转录酶第210位的亮氨酸在体内突变为色氨酸会导致对3'-叠氮-3'-脱氧胸苷产生高水平耐药性。
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引用本文的文献

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J Exp Med. 2001 Feb 5;193(3):375-86. doi: 10.1084/jem.193.3.375.
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Relative replication fitness of a high-level 3'-azido-3'-deoxythymidine-resistant variant of human immunodeficiency virus type 1 possessing an amino acid deletion at codon 67 and a novel substitution (Thr-->Gly) at codon 69.1型人类免疫缺陷病毒的一种高水平3'-叠氮基-3'-脱氧胸苷抗性变体的相对复制适应性,该变体在密码子67处存在氨基酸缺失,在密码子69处有一个新的替换(苏氨酸→甘氨酸)
J Virol. 2000 Dec;74(23):10958-64. doi: 10.1128/jvi.74.23.10958-10964.2000.
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Convergent evolution of reverse transcriptase (RT) genes of human immunodeficiency virus type 1 subtypes E and B following nucleoside analogue RT inhibitor therapies.
核苷类似物逆转录酶抑制剂治疗后,人类免疫缺陷病毒1型E亚型和B亚型逆转录酶(RT)基因的趋同进化。
J Virol. 2000 Jun;74(11):5357-62. doi: 10.1128/jvi.74.11.5357-5362.2000.
4
Sequence analysis of the polymerase domain of HIV-1 reverse transcriptase in naive and zidovudine-treated individuals reveals a higher polymorphism in alpha-helices as compared with beta-strands.对未接受治疗和接受齐多夫定治疗的个体中HIV-1逆转录酶聚合酶结构域的序列分析显示,与β链相比,α螺旋中的多态性更高。
Virus Genes. 1999;18(3):203-10. doi: 10.1023/a:1008012101219.
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Relative replicative fitness of zidovudine-resistant human immunodeficiency virus type 1 isolates in vitro.齐多夫定耐药的1型人类免疫缺陷病毒分离株在体外的相对复制适应性
J Virol. 1998 May;72(5):3773-8. doi: 10.1128/JVI.72.5.3773-3778.1998.
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An in vivo mutation from leucine to tryptophan at position 210 in human immunodeficiency virus type 1 reverse transcriptase contributes to high-level resistance to 3'-azido-3'-deoxythymidine.人类免疫缺陷病毒1型逆转录酶第210位的亮氨酸在体内突变为色氨酸会导致对3'-叠氮-3'-脱氧胸苷产生高水平耐药性。
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7
Zidovudine resistance is suppressed by mutations conferring resistance of human immunodeficiency virus type 1 to foscarnet.齐多夫定耐药性可被赋予人类免疫缺陷病毒1型对膦甲酸钠耐药性的突变所抑制。
J Virol. 1996 Oct;70(10):7171-81. doi: 10.1128/JVI.70.10.7171-7181.1996.