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Resistance to nucleoside analogs of selective mutants of human immunodeficiency virus type 2 reverse transcriptase.人免疫缺陷病毒2型逆转录酶选择性突变体对核苷类似物的耐药性。
J Virol. 1995 Jan;69(1):509-12. doi: 10.1128/JVI.69.1.509-512.1995.
2
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J Virol. 1992 Dec;66(12):7568-71. doi: 10.1128/JVI.66.12.7568-7571.1992.
3
The fidelity of misinsertion and mispair extension throughout DNA synthesis exhibited by mutants of the reverse transcriptase of human immunodeficiency virus type 2 resistant to nucleoside analogs.对核苷类似物耐药的2型人类免疫缺陷病毒逆转录酶突变体在整个DNA合成过程中错掺入和错配延伸的保真度。
Eur J Biochem. 1997 Nov 15;250(1):106-14. doi: 10.1111/j.1432-1033.1997.00106.x.
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FEBS Lett. 1995 Aug 14;370(1-2):59-62. doi: 10.1016/0014-5793(95)00793-9.
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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.1型人类免疫缺陷病毒（HIV-1）逆转录酶（RT）的喹喔啉非核苷抑制剂对HIV-1复制的选择性压力导致核苷RT抑制剂特异性（RT Leu-74→Val或Ile以及Val-75→Leu或Ile）HIV-1突变体的出现。
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Enzymatic properties and sensitivity to inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase with Glu-138-->Arg and Tyr-188-->His mutations.具有Glu-138→Arg和Tyr-188→His突变的人类免疫缺陷病毒1型（HIV-1）逆转录酶的酶学特性及对抑制剂的敏感性
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Transmitted drug resistance, selection of resistance mutations and moderate antiretroviral efficacy in HIV-2: analysis of the HIV-2 Belgium and Luxembourg database.HIV-2中的传播耐药性、耐药突变的选择及中等抗逆转录病毒疗效：对比利时和卢森堡HIV-2数据库的分析
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J Clin Microbiol. 2000 Apr;38(4):1370-4. doi: 10.1128/JCM.38.4.1370-1374.2000.
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3'-Azido-3'-deoxythymidine drug resistance mutations in HIV-1 reverse transcriptase can induce long range conformational changes.人类免疫缺陷病毒-1逆转录酶中的3'-叠氮基-3'-脱氧胸苷耐药性突变可诱导远距离构象变化。
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Reactivation of thymidine kinase-defective herpes simplex virus is enhanced by nucleoside.核苷可增强胸苷激酶缺陷型单纯疱疹病毒的复活。
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Population migration and the spread of types 1 and 2 human immunodeficiency viruses.人口迁移与1型和2型人类免疫缺陷病毒的传播
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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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Crystal structure of human immunodeficiency virus type 1 reverse transcriptase complexed with double-stranded DNA at 3.0 A resolution shows bent DNA.人类免疫缺陷病毒1型逆转录酶与双链DNA复合物在3.0埃分辨率下的晶体结构显示出弯曲的DNA。
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Mechanism of resistance of human immunodeficiency virus type 1 to 2',3'-dideoxyinosine.1型人类免疫缺陷病毒对2'，3'-双脱氧肌苷的耐药机制。
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Sensitivity of wild-type human immunodeficiency virus type 1 reverse transcriptase to dideoxynucleotides depends on template length; the sensitivity of drug-resistant mutants does not.野生型人类免疫缺陷病毒1型逆转录酶对双脱氧核苷酸的敏感性取决于模板长度；耐药突变体的敏感性则不然。
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6
Mutagenic study of codons 74 and 215 of the human immunodeficiency virus type 1 reverse transcriptase, which are significant in nucleoside analog resistance.对1型人类免疫缺陷病毒逆转录酶第74和215密码子的诱变研究，这两个密码子在核苷类似物耐药性方面具有重要意义。
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Sensitivity of HIV-1 reverse transcriptase and its mutants to inhibition by azidothymidine triphosphate.人类免疫缺陷病毒1型逆转录酶及其突变体对叠氮胸苷三磷酸抑制作用的敏感性。
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HIV resistance to reverse transcriptase inhibitors.人类免疫缺陷病毒对逆转录酶抑制剂的耐药性。
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9
Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS.从艾滋病患者和有患艾滋病风险的人群中频繁检测和分离出细胞病变逆转录病毒（HTLV-III）。
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Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS).从一名有获得性免疫缺陷综合征（艾滋病）风险的患者体内分离出一种嗜T淋巴细胞逆转录病毒。
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人免疫缺陷病毒2型逆转录酶选择性突变体对核苷类似物的耐药性。

Resistance to nucleoside analogs of selective mutants of human immunodeficiency virus type 2 reverse transcriptase.

作者信息

Perach M, Rubinek T, Hizi A

机构信息

Department of Cell Biology and Histology, Sickler School of Medicine, Tel Aviv University, Israel.

出版信息

J Virol. 1995 Jan;69(1):509-12. doi: 10.1128/JVI.69.1.509-512.1995.

DOI:10.1128/JVI.69.1.509-512.1995
PMID:7527086
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC188600/
Abstract

We have studied selected mutants of human immunodeficiency virus type 2 (HIV-2) reverse transcriptase (RT) in a cell-free system in order to assess whether the mutant proteins exhibit a reduction in the sensitivity to nucleoside analog inhibitors similar to that of HIV-1 RT. We have modified, by site-directed mutagenesis, several of those amino acid residues so that their equivalent substitutions in HIV-1 RT have led to the formation of HIV-1 RT variants with the highest degree of resistance to dideoxynucleoside triphosphates (i.e., Glu-89-->Gly, Leu-74-->Val, and Ser-215-->Tyr [which is comparable to the Thr-215-->Tyr mutation of HIV-1 RT] and the double mutations Glu-89-->Gly/Ser-215-->Tyr and and Leu-74-->Val/Ser-215-->Tyr). The similarity found between resistance of the newly generated HIV-2 RT mutants to nucleoside analogs and that of the comparable mutants of HIV-1 RT can support the notion that the overall protein folding around the DNA polymerase active site in HIV-2 RT is quite similar to that of HIV-1 RT.

摘要

我们在无细胞系统中研究了人类免疫缺陷病毒2型（HIV-2）逆转录酶（RT）的特定突变体，以评估这些突变蛋白对核苷类似物抑制剂的敏感性是否降低，类似于HIV-1 RT。我们通过定点诱变修饰了其中几个氨基酸残基，使得它们在HIV-1 RT中的等效取代导致形成了对双脱氧核苷三磷酸具有最高抗性的HIV-1 RT变体（即，Glu-89→Gly、Leu-74→Val和Ser-215→Tyr [这与HIV-1 RT的Thr-215→Tyr突变相当] 以及双突变Glu-89→Gly/Ser-215→Tyr和Leu-74→Val/Ser-215→Tyr）。新产生的HIV-2 RT突变体对核苷类似物的抗性与HIV-1 RT的可比突变体之间的相似性可以支持这样一种观点，即HIV-2 RT中DNA聚合酶活性位点周围的整体蛋白质折叠与HIV-1 RT非常相似。