title: 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.
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.
authors.affiliation: Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium. dirk.daelemans@rega.kuleuven.be
authors.forename: Dirk
authors.initials: D
authors.lastname: Daelemans
authors.forename: Richard
authors.initials: R
authors.lastname: Lu
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.forename: Alan
authors.initials: A
authors.lastname: Engelman
mesh_terms: D006678:HIV / Q000187:drug effects* / Q000235:genetics*; D019428:HIV Integrase Inhibitors / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods*; D013539:Simian virus 40 / Q000235:genetics*
chemical_list: D019428:HIV Integrase Inhibitors