Stevens Miguel, Pollicita Michela, Pannecouque Christophe, Verbeken Erik, Tabarrini Oriana, Cecchetti Violetta, Aquaro Stefano, Perno Carlo Federico, Fravolini Arnaldo, De Clercq Erik, Schols Dominique, Balzarini Jan
Rega Institute for Medical Research, Katholieke Universiteit Leuven, and Division of Histopathology, University Hospitals, Leuven, Belgium.
Antimicrob Agents Chemother. 2007 Apr;51(4):1407-13. doi: 10.1128/AAC.01251-06. Epub 2007 Jan 22.
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.
对两种新型6-去氟喹诺酮衍生物HM-12和HM-13在急性、慢性和潜伏性1型人类免疫缺陷病毒（HIV-1）感染的细胞培养物中的抗人类免疫缺陷病毒（抗HIV）活性进行了评估，发现它们表现为有效的HIV-1转录抑制剂。为了在体内扩展这一结果，我们基于移植了潜伏性HIV-1感染的早幼粒细胞OM-10.1细胞的SCID小鼠，开发了一种用于HIV-1潜伏的人工人源化SCID小鼠模型，其中HIV-1可通过给予人肿瘤坏死因子α（hTNF-α）在体内重新激活。在hTNF-α刺激之前用HM-12或HM-13处理这些SCID小鼠，对病毒重新激活产生了显著的抑制作用。由于这两种喹诺酮衍生物都能够在体内抑制来自这个人造病毒库的HIV-1重新激活，我们为喹诺酮类药物用于控制HIV-1感染提供了令人鼓舞的证据。
