TRIPLEX-MEDIATED INHIBITION OF HIV DNA INTEGRATION IN-VITRO

Integration of human immunodeficiency virus (HIV) DNA into the genome of host cells is an obligatory step in the replicative cycle of the vi rus. The overall process is carried out in vitro by a single viral pro tein, the integrase, which binds to short sequences located at the end s of viral DNA long terminal repeats (LTRs). These end sequences are h ighly conserved in all HIV genomes and are therefore attractive target s for selective DNA binding compounds. The integrase-binding site loca ted in U3 LTR contains a purine motif, 5'-GGAAGGG-3' which can be sele ctively targeted by oligonucleotide-intercalator conjugates. Under neu tral pH and physiological temperature, these conjugates readily form a stable complex with the viral DNA which involves a short DNA tripler. Triple-helix formation prevents the catalytic functions of the integr ase in vitro which results in a sequence-specific inhibition of the U3 integration process.