8.HIV-1感染モデル : ―免疫不全マウスを用いた疾患モデル―

概要

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We established seven new mouse strains with defective T and B cells as well as innate immunological reactions, and showed that six mutant mouse strains efficiently received human PBL engraftment (hu-PBL-mouse) . Increased levels of macrophage-tropic and T-cell line-tropic HIV-1 replication were observed in the new hu-PBL-mice. In one particular strain, hu-PBL-NOD-scid, high levels of HIV-1 viremia (10<SUP>6</SUP> infectious units per milliliter) were detected after inoculation of the virus. The viral load was about 1000 times higher than that observed in other HIV-1 infected hu-PBL-mice. Although high viremia did not correlate with the total amount of HIV-1 RNA in cells from infected mice, high levels of free virions were detected in only hu-PBL-NOD-scid mice. HIV-1 viremia induced systemic HIV-1 infection involving the liver, lymph nodes, and brain. PCR <I>in situ</I> hybridization confirmed that HIV-1 infected cells invaded mouse brain tissue. The present study indicates that the immunological response of the NOD-scid mouse is inadequate to protect the animal against severe systemic infection. Our results suggest that the genetic background, including innate immunity, is critical in the development of primary HIV-1 viremia and subsequent CNS invasion. The NOD-scid mouse represents a useful model for the study of the pathogenesis, especially brain involvement, and therapy of primary HIV-1 viremia.