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
- 15 April 2007
- journal article
- research article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 81 (8), 4381-4385
- https://doi.org/10.1128/jvi.02637-06
Abstract
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.Keywords
This publication has 31 references indexed in Scilit:
- Development of a Human Immunodeficiency Virus Vector-Based, Single-Cycle Assay for Evaluation of Anti-Integrase CompoundsAntimicrobial Agents and Chemotherapy, 2006
- Novel HIV-1 Integrase Inhibitors Derived from Quinolone AntibioticsJournal of Medicinal Chemistry, 2006
- Enzymology of a carbonyl reduction clearance pathway for the HIV integrase inhibitor, S-1360: role of human liver cytosolic aldo-keto reductasesChemico-Biological Interactions, 2004
- Simian Virus 40-Based Replication of Catalytically Inactive Human Immunodeficiency Virus Type 1 Integrase Mutants in Nonpermissive T Cells and Monocyte-Derived MacrophagesJournal of Virology, 2004
- Human Immunodeficiency Virus Type 1 Replication in the Absence of Integrase-Mediated DNA Recombination: Definition of Permissive and Nonpermissive T-Cell LinesJournal of Virology, 2001
- 6-Aminoquinolones as New Potential Anti-HIV AgentsJournal of Medicinal Chemistry, 2000
- Inhibition of HIV-1 Replication by a Nonnucleoside Reverse Transcriptase InhibitorScience, 1990
- Potent and selective inhibition of HIV-1 replication in vitro by a novel series of TIBO derivativesNature, 1990
- Dextran Sulfate Suppression of Viruses in the HIV Family: Inhibition of Virion Binding to CD4 + CellsScience, 1988
- Detection, Isolation, and Continuous Production of Cytopathic Retroviruses (HTLV-III) from Patients with AIDS and Pre-AIDSScience, 1984