title: Novel in vivo model for the study of human immunodeficiency virus type 1 transcription inhibitors: evaluation of new 6-desfluoroquinolone derivatives.
abstract: Two novel 6-desfluoroquinolone derivatives, HM-12 and HM-13, were evaluated for anti-human immunodeficiency virus (anti-HIV) activity in acutely, chronically, and latently HIV type 1 (HIV-1)-infected cell cultures and were found to behave as potent HIV-1 transcription inhibitors. In order to extend this result in vivo, we developed an artificial hu-SCID mouse model for HIV-1 latency based on SCID mice engrafted with latently HIV-1-infected promyelocytic OM-10.1 cells in which HIV-1 can be reactivated in vivo by the administration of human tumor necrosis factor alpha (hTNF-alpha). Treating these SCID mice with HM-12 or HM-13 prior to hTNF-alpha stimulation resulted in a pronounced suppressive effect on viral reactivation. Since both quinolone derivatives were able to inhibit the reactivation of HIV-1 from this artificial viral reservoir in vivo, we provide encouraging evidence for the use of quinolones in the control of HIV-1 infections.
authors.affiliation: Rega Institute for Medical Research, Katholieke Universiteit Leuven, and Division of Histopathology, University Hospitals, Leuven, Belgium.
authors.forename: Miguel
authors.initials: M
authors.lastname: Stevens
authors.forename: Michela
authors.initials: M
authors.lastname: Pollicita
authors.forename: Christophe
authors.initials: C
authors.lastname: Pannecouque
authors.forename: Erik
authors.initials: E
authors.lastname: Verbeken
authors.forename: Oriana
authors.initials: O
authors.lastname: Tabarrini
authors.forename: Violetta
authors.initials: V
authors.lastname: Cecchetti
authors.forename: Stefano
authors.initials: S
authors.lastname: Aquaro
authors.forename: Carlo Federico
authors.initials: CF
authors.lastname: Perno
authors.forename: Arnaldo
authors.initials: A
authors.lastname: Fravolini
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.forename: Dominique
authors.initials: D
authors.lastname: Schols
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D004195:Disease Models, Animal; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D008954:Models, Biological; D015363:Quinolones / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; C521529:HM-12 compound; C521530:HM-13 compound; D015363:Quinolones