Suppression of HIV Infection in AZT-Treated SCID-hu Mice

Abstract

The SCID-hu mouse, engrafted with human hematolymphoid organs, is permissive for infection with the human immunodeficiency virus (HIV). This mouse model was used to test compounds for antiviral efficacy. Two weeks after infection with HIV, 100 percent (40/40) of SCID-hu mice were positive for HIV by the polymerase chain reaction. When first treated with 3'-azido-3'-deoxythymidine (AZT), none (0/17) were HIV-positive by this assay. However, AZT-treated SCID-hu mice did have a few infected cells; after AZT treatment was stopped, viral spread was detected by polymerase chain reaction in such mice. Thus, the SCID-hu mouse provides a means to directly compare new antiviral compounds with AZT and to further improve antiviral efficacy.

Retroviral sequences related to human T-lymphotropic virus type II in patients with chronic fatigue immune dysfunction syndrome.

“…Amplified DNA was stored at -20°C until use. The template capability of purified DNA was verified by performing a PCR using /3-globin primers (19 (17) at 37°C. The filters were exposed to Kodak XAR film for 5-7 days at -70°C.…”

Human antibodies that neutralize primary human immunodeficiency virus type 1 in vitro do not provide protection in an in vivo model

“…E. Osterhaus. Fax + 31 10 4365145, e-mail Osterhaus@viro.fgg.eur.nl haematopoietic tissue into SCID mice (Mosier et al, 1991;Namikawa eta]., 1988); subsequently, the activated human graft is infected with HIV-1. In these models it was demonstrated that polyclonal hyperimmune globulins from seropositive donors (HIVIG), a monoclonal antibody (MAb) directed against the V3 loop on HIV-1 gp120 and 3'-azido-2',3'-dideoxythymidine (AZT) inhibited the replication of T cell line-adapted (TCLA) HIV-1 strains (Safrit et al, 1993;Shih et at., 1991;McCune et al, 1990). In infected individuals HIV-I has been shown to replicate predominantly in activated macrophages and T lymphocytes resulting in high virus loads in lymphoid organs (Embretson et al, 1993;Pantaleo et al, 1993).…”

Engraftment and long-term expression of human fetal hemopoietic stem cells in sheep following transplantation in utero.

“…HLA matching and T cell depletion ofthe donor graft are also useful adjuncts to mitigate development of life-threatening graft versus host disease (GVHD) which may occur during graft rejection (1,2). When applied appropriately, these procedures have been used to achieve chimerism between different species including humanmouse (4)(5)(6)(7)(8)(9)(10). Xenogeneic transplantation ofhuman HSC has also been reported in genetically deficient mice (5)(6)(7)(8)(9)(10) and in normal mice rendered tolerant by lethal irradiation (4).…”

“…Tolerance oftransplanted allogeneic cells in clinical settings can be achieved using genetically immunodeficient donors/recipients (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). Alternatively, immunocompetent recipients can be rendered immunotolerant by using immunosuppressive and/or cytoablative procedures, which may also serve to promote engraftment by donor HSC by eliminating recipient HSC which may compete for homing sites within the bone marrow (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). HLA matching and T cell depletion ofthe donor graft are also useful adjuncts to mitigate development of life-threatening graft versus host disease (GVHD) which may occur during graft rejection (1,2).…”