braco-19 and HIV-Infections

Altered telomere maintenance mechanism (TMM) is linked to increased DNA damage at telomeres and telomere uncapping. We previously showed that HIV-1 latent cells have altered TMM and are susceptible to ligands that target G-quadruplexes (G4) at telomeres. Susceptibility of latent cells to telomere targeting could potentially be used to support approaches to eradicate HIV reservoirs. However, G4 ligands also target G-quadruplexes in promoters blocking gene transcription. Since HIV promoter sequence can form G-quadruplexes, we investigated whether G4 ligands interfere with HIV-1 promoter activity and virus reactivation from latency, and whether telomere targeting could be combined with latency reversing agents (LRAs) to promote elimination of HIV reservoirs. Our results indicate that Sp1 binding region in HIV-1 promoter can adopt G4 structures in duplex DNA, and that

Topics: Acridines; Anti-HIV Agents; Apoptosis; Bryostatins; CD4-Positive T-Lymphocytes; DNA Damage; DNA Mismatch Repair; DNA Repair; Drug Synergism; Drug Therapy, Combination; G-Quadruplexes; HIV Infections; HIV-1; Host-Pathogen Interactions; Humans; Jurkat Cells; Ligands; Porphyrins; Promoter Regions, Genetic; Telomere; Telomere Homeostasis; Virus Activation; Virus Latency; Vorinostat