1型人类免疫缺陷病毒（HIV-1）蛋白酶变体的细胞内表达可抑制野生型和蛋白酶抑制剂耐药型HIV-1毒株在人T细胞系中的复制。
Intracellular expression of human immunodeficiency virus type 1 (HIV-1) protease variants inhibits replication of wild-type and protease inhibitor-resistant HIV-1 strains in human T-cell lines.
作者信息
Junker U, Escaich S, Plavec I, Baker J, McPhee F, Rose J R, Craik C S, Böhnlein E
机构信息
Progenesys Program at Systemix, Palo Alto, California 94304, USA.
出版信息
J Virol. 1996 Nov;70(11):7765-72. doi: 10.1128/JVI.70.11.7765-7772.1996.
Abstract
The enzymatic activity of the human immunodeficiency type 1 (HIV-1) protease (PR) is crucial to render HIV-1 virions mature and infectious. Hence, genetic intervention strategies based on trans-dominant (td) variants of the HIV-1 PR might be an alternative to current pharmacological and gene therapy regimens for AIDS. CD4-positive human CEM-SS T-cell lines were generated which constitutively expressed HIV-1 td PR variants. HIV-1 infection experiments demonstrated severely reduced HIV-1 replication in these td PR CEM-SS cell lines compared with control T cells expressing wild-type PR. Furthermore, replication of an HIV-1 isolate bearing a PR inhibitor-resistant PR was blocked, showing that genetic intervention strategies based on td PRs can be effective against HIV-1 isolates containing PR inhibitor-resistant mutants.
摘要
人类免疫缺陷病毒1型（HIV-1）蛋白酶（PR）的酶活性对于使HIV-1病毒体成熟并具有传染性至关重要。因此，基于HIV-1 PR的反式显性（td）变体的基因干预策略可能是目前用于治疗艾滋病的药理学和基因治疗方案的替代方法。构建了持续表达HIV-1 td PR变体的CD4阳性人类CEM-SS T细胞系。HIV-1感染实验表明，与表达野生型PR的对照T细胞相比，这些td PR CEM-SS细胞系中的HIV-1复制严重减少。此外，携带对PR抑制剂耐药的PR的HIV-1分离株的复制被阻断，这表明基于td PRs的基因干预策略可有效对抗含有PR抑制剂耐药突变体的HIV-1分离株。
相似文献
1
Intracellular expression of human immunodeficiency virus type 1 (HIV-1) protease variants inhibits replication of wild-type and protease inhibitor-resistant HIV-1 strains in human T-cell lines.1型人类免疫缺陷病毒（HIV-1）蛋白酶变体的细胞内表达可抑制野生型和蛋白酶抑制剂耐药型HIV-1毒株在人T细胞系中的复制。
J Virol. 1996 Nov;70(11):7765-72. doi: 10.1128/JVI.70.11.7765-7772.1996.
2
Individual contributions of mutant protease and reverse transcriptase to viral infectivity, replication, and protein maturation of antiretroviral drug-resistant human immunodeficiency virus type 1.突变蛋白酶和逆转录酶对耐抗逆转录病毒药物的1型人类免疫缺陷病毒的病毒感染性、复制及蛋白质成熟的个体贡献。
J Virol. 2001 Apr;75(7):3291-300. doi: 10.1128/JVI.75.7.3291-3300.2001.
3
Potent inhibition of human immunodeficiency virus type 1 (HIV-1) replication by inducible expression of HIV-1 PR multimers.通过诱导表达HIV-1蛋白酶多聚体对人类免疫缺陷病毒1型（HIV-1）复制的强效抑制
J Virol. 1995 Oct;69(10):5988-94. doi: 10.1128/JVI.69.10.5988-5994.1995.
4
Impaired replication of protease inhibitor-resistant HIV-1 in human thymus.蛋白酶抑制剂耐药性HIV-1在人胸腺中的复制受损。
Nat Med. 2001 Jun;7(6):712-8. doi: 10.1038/89090.
5
Characterization of human immunodeficiency virus type 1 variants with increased resistance to a C2-symmetric protease inhibitor.对1型人类免疫缺陷病毒对一种C2对称蛋白酶抑制剂耐药性增加的变体的特征分析。
J Virol. 1994 Mar;68(3):2016-20. doi: 10.1128/JVI.68.3.2016-2020.1994.
6
7
Non-infectious fluorimetric assay for phenotyping of drug-resistant HIV proteinase mutants.用于耐药性HIV蛋白酶突变体表型分析的非感染性荧光测定法。
J Clin Virol. 2006 May;36(1):50-9. doi: 10.1016/j.jcv.2006.01.014. Epub 2006 Mar 9.
8
Human immunodeficiency virus type 1 viral background plays a major role in development of resistance to protease inhibitors.1型人类免疫缺陷病毒的病毒背景在对蛋白酶抑制剂耐药性的产生中起主要作用。
Proc Natl Acad Sci U S A. 1996 Feb 20;93(4):1648-53. doi: 10.1073/pnas.93.4.1648.
9
Construction of a novel SHIV having an HIV-1-derived protease gene and its infection to rhesus macaques: a useful tool for in vivo efficacy tests of protease inhibitors.
Microbes Infect. 2007 Apr;9(4):475-82. doi: 10.1016/j.micinf.2007.01.005. Epub 2007 Jan 21.
10
HIV-1 protease dimer interface mutations that compensate for viral reverse transcriptase instability in infectious virions.在感染性病毒粒子中补偿病毒逆转录酶不稳定性的HIV-1蛋白酶二聚体界面突变。
J Mol Biol. 2007 Sep 14;372(2):369-81. doi: 10.1016/j.jmb.2007.06.073. Epub 2007 Jul 3.
引用本文的文献
1
Targeting human immunodeficiency virus type 1 assembly, maturation and budding.靶向1型人类免疫缺陷病毒的组装、成熟和出芽。
Drug Target Insights. 2007;2:159-82. Epub 2007 Jul 20.
2
HIV-1 protease has a genetic T-cell adjuvant effect which is negatively regulated by proteolytic activity.HIV-1 蛋白酶具有遗传 T 细胞佐剂效应，该效应受蛋白酶活性的负调控。
J Virol. 2010 Aug;84(15):7743-9. doi: 10.1128/JVI.00747-10. Epub 2010 May 19.
3
Novel macromolecular inhibitors of human immunodeficiency virus-1 protease.新型人类免疫缺陷病毒-1蛋白酶大分子抑制剂
Protein Eng Des Sel. 2008 Jul;21(7):453-61. doi: 10.1093/protein/gzn022. Epub 2008 May 13.
4
Maintenance of the Gag/Gag-Pol ratio is important for human immunodeficiency virus type 1 RNA dimerization and viral infectivity.维持Gag/Gag-Pol比率对于1型人类免疫缺陷病毒的RNA二聚化和病毒感染性很重要。
J Virol. 2001 Feb;75(4):1834-41. doi: 10.1128/JVI.75.4.1834-1841.2001.
5
The protease and the assembly protein of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8).卡波西肉瘤相关疱疹病毒（人类疱疹病毒8型）的蛋白酶和装配蛋白
J Virol. 1997 Sep;71(9):7030-8. doi: 10.1128/JVI.71.9.7030-7038.1997.
本文引用的文献
1
Detection of intracellular HIV-1 Rev protein by flow cytometry.通过流式细胞术检测细胞内HIV-1 Rev蛋白。
J Immunol Methods. 1995 Dec 27;188(2):187-95. doi: 10.1016/0022-1759(95)00237-5.
2
Comparison of trans-dominant inhibitory mutant human immunodeficiency virus type 1 genes expressed by retroviral vectors in human T lymphocytes.逆转录病毒载体在人T淋巴细胞中表达的反式显性抑制突变型人类免疫缺陷病毒1型基因的比较。
J Virol. 1993 Jun;67(6):3199-207. doi: 10.1128/JVI.67.6.3199-3207.1993.
3
A Rev-inducible mutant gag gene stably transferred into T lymphocytes: an approach to gene therapy against human immunodeficiency virus type 1 infection.一种稳定转入T淋巴细胞的Rev诱导型突变gag基因：一种针对1型人类免疫缺陷病毒感染的基因治疗方法。
Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3657-61. doi: 10.1073/pnas.91.9.3657.
4
A molecular genetic intervention for AIDS--effects of a transdominant negative form of Rev.一种针对艾滋病的分子遗传学干预措施——反式显性负性Rev蛋白的作用
Hum Gene Ther. 1994 Jan;5(1):79-92. doi: 10.1089/hum.1994.5.1-79.
5
Selection and analysis of human immunodeficiency virus type 1 variants with increased resistance to ABT-538, a novel protease inhibitor.对新型蛋白酶抑制剂ABT-538耐药性增强的1型人类免疫缺陷病毒变体的筛选与分析
J Virol. 1995 Feb;69(2):701-6. doi: 10.1128/JVI.69.2.701-706.1995.
6
Effects of second-site mutations on dominant interference by a human immunodeficiency virus type 1 envelope glycoprotein mutant.第二位点突变对1型人类免疫缺陷病毒包膜糖蛋白突变体显性干扰的影响。
J Virol. 1995 Feb;69(2):1344-8. doi: 10.1128/JVI.69.2.1344-1348.1995.
7
In vivo emergence of HIV-1 variants resistant to multiple protease inhibitors.对多种蛋白酶抑制剂耐药的HIV-1变体在体内的出现。
Nature. 1995 Apr 6;374(6522):569-71. doi: 10.1038/374569a0.
8
RevM10-mediated inhibition of HIV-1 replication in chronically infected T cells.
Hum Gene Ther. 1995 May;6(5):625-34. doi: 10.1089/hum.1995.6.5-625.
9
Defining the level of human immunodeficiency virus type 1 (HIV-1) protease activity required for HIV-1 particle maturation and infectivity.确定1型人类免疫缺陷病毒（HIV-1）蛋白酶活性水平，该活性是HIV-1颗粒成熟和感染性所必需的。
J Virol. 1995 May;69(5):2751-8. doi: 10.1128/JVI.69.5.2751-2758.1995.
10
Trans-dominant inhibitory human immunodeficiency virus type 1 protease monomers prevent protease activation and virion maturation.反式显性抑制性人类免疫缺陷病毒1型蛋白酶单体可阻止蛋白酶激活和病毒体成熟。
Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10069-73. doi: 10.1073/pnas.92.22.10069.
Zotero 插件