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  • Title: Inhibition of human immunodeficiency virus (HIV-1) infection in human peripheral blood leucocytes-SCID reconstituted mice by rapamycin.
    Author: Nicoletti F, Lapenta C, Donati S, Spada M, Ranazzi A, Cacopardo B, Mangano K, Belardelli F, Perno C, Aquaro S.
    Journal: Clin Exp Immunol; 2009 Jan; 155(1):28-34. PubMed ID: 19076826.
    Abstract:
    The capacity of the immunomodulatory drug rapamycin (RAPA) to inhibit replication of the CCR5 strain of human immunodeficiency virus (HIV) in vitro prompted us to test its effects in a murine preclinical model of HIV infection. RAPA (0.6 or 6 mg/kg body weight) or its vehicle were administered daily, per os, to SCID mice reconstituted with human peripheral blood leucocytes (hu-PBL) starting 2 days before the intraperitoneal challenge with the R5 tropic SF162 strain of HIV-1 (1000 50% tissue culture infective dose/ml). Relative to hu-PBL-SCID mice that received no treatment, HIV-infected hu-PBL-SCID mice treated with the vehicle control for 3 weeks exhibited a severe depletion of CD4(+) cells (90%), an increase in CD8(+) cells and an inversion of the CD4(+)/CD8(+) cell ratio. In contrast, treatment of HIV-infected mice with RAPA prevented a decrease in CD4(+) cells and the increase of CD8(+) cells, thereby preserving the original CD4(+):CD8(+) cell ratio. Viral infection also resulted in the detection of HIV-DNA within peritoneal cells and spleen, and lymph node tissues of the vehicle-treated mice within 3 weeks of the viral challenge. In contrast, treatment with RAPA decreased cellular provirus integration and reduced HIV-RNA levels in the blood. Furthermore, in co-cultivation assays, spleens from RAPA-treated mice exhibited a reduced capacity for infecting allogeneic T cells which was dose-dependent. These data show that RAPA possesses powerful anti-viral activity against R5 strains of HIV in vivo and support the use of additional studies to evaluate the potential application of this drug in the management of HIV patients.
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