Characterization of a replication-competent, integrase-defective human immunodeficiency virus (HIV)/simian virus 40 chimera as a powerful tool for the discovery and validation of HIV integrase inhibitors

被引：20

作者：

Daelemans, Dirk

Lu, Richard

De Clercq, Erik

Engelman, Alan

机构：

[1] Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Louvain, Belgium

[2] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Div AIDS, Boston, MA 02115 USA

来源：

JOURNAL OF VIROLOGY | 2007年 / 81卷 / 08期

关键词：

D O I：

10.1128/JVI.02637-06

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Integrase is actively studied as an antiviral target, but many inhibitors selected from biochemical screens fail to inhibit human immunodeficiency virus (HIV) replication or primarily affect off-site targets. Here we develop and validate a replication-competent, simian virus 40-HIV integrase mutant chimera as a novel tool to classify the mechanism of action of potential integrase inhibitors. Whereas the mutant was more susceptible than the wild type to entry, reverse transcriptase, and protease inhibitors, it specifically resisted the action of integrase inhibitor L-870,810. We furthermore demonstrate inhibition of integration by GS-9137 and GS-9160 and off-site targeting by the 6-aminoquinolone antibiotic WM-5.

引用

页码：4381 / 4385

页数：5

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