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
Journal of Virology vol:81 issue:8 pages:4381-4385
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 (SV40)-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 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.