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Antimicrobial Agents and Chemotherapy, April 2007, p. 1407-1413, Vol. 51, No. 4
0066-4804/07/$08.00+0     doi:10.1128/AAC.01251-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Novel In Vivo Model for the Study of Human Immunodeficiency Virus Type 1 Transcription Inhibitors: Evaluation of New 6-Desfluoroquinolone Derivatives{triangledown}

Miguel Stevens,1 Michela Pollicita,5 Christophe Pannecouque,1 Erik Verbeken,2 Oriana Tabarrini,3 Violetta Cecchetti,3 Stefano Aquaro,4,5 Carlo Federico Perno,5 Arnaldo Fravolini,3 Erik De Clercq,1 Dominique Schols,1 and Jan Balzarini1*

Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium,1 Division of Histopathology, University Hospitals, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium,2 Department of Chemistry and Technology of Drug, University of Perugia, Via del Liceo, 06123 Perugia, Italy,3 Department of Pharmaco-Biology, University of Calabria, 87030 Rende (CS), Italy,4 Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy5

Received 5 October 2006/ Returned for modification 17 November 2006/ Accepted 8 January 2007

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.

* Corresponding author. Mailing address: Rega Institute for Medical Research, Minderbroedersstraat 10, B-3000 Leuven, Belgium. Phone: 32-16-332181. Fax: 32-16-337340. E-mail: jan.balzarini{at}rega.kuleuven.be

{triangledown} Published ahead of print on 22 January 2007.

Antimicrobial Agents and Chemotherapy, April 2007, p. 1407-1413, Vol. 51, No. 4
0066-4804/07/$08.00+0     doi:10.1128/AAC.01251-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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