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

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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

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HIV-1
SCID Mice
Quinolones
Tumor Necrosis Factor-alpha
HIV Infections
Cell Culture Techniques
HIV

ASJC Scopus subject areas

  • Pharmacology (medical)

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

In: Antimicrobial Agents and Chemotherapy, Vol. 51, No. 4, 04.2007, p. 1407-1413.

Research output: Contribution to journalArticle

Stevens, M, Pollicita, M, Pannecouque, C, Verbeken, E, Tabarrini, O, Cecchetti, V, Aquaro, S, Perno, CF, 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, vol. 51, no. 4, pp. 1407-1413. https://doi.org/10.1128/AAC.01251-06
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. / Novel in vivo model for the study of human immunodeficiency virus type 1 transcription inhibitors : Evaluation of new 6-desfluoroquinolone derivatives. In: Antimicrobial Agents and Chemotherapy. 2007 ; Vol. 51, No. 4. pp. 1407-1413.
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