Novel in vivo model for the study of human immunodeficiency virus type 1 transcription inhibitors: Evaluation of new 6-desfluoroquinolone derivatives

Miguel Stevens, Michela Pollicita, Christophe Pannecouque, Erik Verbeken, Oriana Tabarrini, Violetta Cecchetti, Stefano Aquaro, Carlo Federico Perno, Arnaldo Fravolini, Erik De Clercq, Dominique Schols, Jan Balzarini

Research output: Contribution to journalArticle

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-α). Treating these SCID mice with HM-12 or HM-13 prior to hTNF-α 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.

Original languageEnglish
Pages (from-to)1407-1413
Number of pages7
JournalAntimicrobial Agents and Chemotherapy
Volume51
Issue number4
DOIs
Publication statusPublished - Apr 2007

ASJC Scopus subject areas

  • Pharmacology (medical)

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    Stevens, M., Pollicita, M., Pannecouque, C., Verbeken, E., Tabarrini, O., Cecchetti, V., Aquaro, S., Perno, C. F., Fravolini, A., De Clercq, E., Schols, D., & Balzarini, J. (2007). Novel in vivo model for the study of human immunodeficiency virus type 1 transcription inhibitors: Evaluation of new 6-desfluoroquinolone derivatives. Antimicrobial Agents and Chemotherapy, 51(4), 1407-1413. https://doi.org/10.1128/AAC.01251-06