Primary human immunodeficiency virus type 1 viremia and central nervous system invasion in a novel hu-PBL-immunodeficient mouse strain

Abstract

We established four new mouse strains with defective T and B cells as well as defects in innate immunological reactions using an NK cell depletion antibody and showed that all mutant mouse strains efficiently received human peripheral blood leukocyte (PBL) engraftment (hu-PBL-scid mice). Higher levels of human immunodeficiency virus type 1 (HIV-1) replication were observed in these new hu-PBL-scid mice than in conventional hu-PBL-C.B-17-scid mice. In one particular strain, hu-PBL-NOD-scid mice, high levels of HIV-1 viremia (more than 10 6 50% infectious doses per ml) were detected after infection with HIV-1. The plasma viral load was about 100 to 1,000 times higher than that observed in other hu-PBL-scid mice infected with HIV-1. Although high-level viremia did not correlate with the total amount of HIV-1 RNA in cells from infected mice, high levels of free virions were detected only in hu-PBL-NOD-scid mice. HIV-1 viremia induced systemic HIV-1 infection involving the liver, lungs, and brain. PCR in situ hybridization confirmed that HIV-1-infected cells invaded the brain tissue of the hu-PBL-NOD-scid mice. Our results suggest that the genetic background, including innate immunity, is critical in the development of primary HIV-1 viremia and subsequent central nervous system invasion with HIV-1. The hu-PBL-NOD-scid mouse represents a useful model for the study of the pathogenesis of HIV-1 in vivo, especially brain involvement, and therapy of primary HIV-1 viremia.

Critical Contribution of Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand (Trail) to Apoptosis of Human Cd4+T Cells in HIV-1–Infected Hu-Pbl-Nod-Scid Mice

“…Reconstitution and HIV-1 Infection of hu-PBL-NOD-SCID Mice. Reconstitution with human PBLs and infection with HIV-1 were performed as previously described (21,22). 1,000 ID 50 of HIV-1 was inoculated intraperitoneally.…”

Reconstitution of human haematopoiesis in non‐obese diabetic/severe combined immunodeficient mice by clonal cells expanded from single CD34+CD38– cells expressing Flk2/Flt3

“…Mice. Experimental NOD/shi-scid (NOD/SCID) mice were obtained from a Central Institute for Experimental Animals (Kawasaki, Japan) (Koyanagi et al, 1997). The mice were kept in microisolator cages on laminar flow racks in a clean experimental room.…”

Hematopoietic Repopulating Ability of Cord Blood CD34+Cells in NOD/Shi‐scidMice

“…Experimental NOD/Shi-scid mice [10] were obtained from the Central Institute for Experimental Animals (Kawasaki, Japan). The NOD/Shi-scid mice were kept in microisolator cages on laminar flow racks in a clean experimental room.…”

“…The NOD/LtSz-scid mouse strain was reported to have a variety of immunological abnormalities such as T-and B-cell deficiency, defective natural killer (NK) cell activity, macrophage dysfunction, and absence of circulating complements [9]. Recently, we also established a xenotransplantation system for human HSC, using NOD/Shi-scid mice, which showed a similar phenotype except the defective NK cell activity [10]. When treated with anti-asialo GM1 antiserum to delete NK cells, the NOD/Shi-scid mice exhibited efficient engraftment of human HSC [11,12].…”