THE SCID-HU MOUSE AS A MODEL FOR HIV-1 INFECTION

DURING normal fetal ontogeny, one of the first organs to harbour CD4-p ositive cells is the thymus1. This organ could therefore be one of the earliest targets infected by human immunodeficiency virus type 1 (HIV -1) in utero. HIV-1-infected cells and pathological abnormalities of t he thymus have been seen in HIV-1-infected adults and children, and in some fetuses aborted from infected women2-5. Studies of HIV-1 pathoge nesis have been hampered by lack of a suitable animal model system. He re we use the SCID-hu mouse6 as a model to investigate the effect of v irus infection on human tissue. The mouse is homozygous for the severe combined immunodeficiency (SCID) defect7,8. The model is constructed by implanting human fetal fiver and thymus under the mouse kidney caps ule. A conjoint human organ develops, which allows normal maturation o f human thymocytes. After direct inoculation of HIV-1 into these impla nts, we observed severe depletion of human CD4-bearing cells within a few weeks of infection. This correlated with increasing virus load in the implants. Thus the SCID-hu mouse may be a useful in vivo system fo r the study of HIV-1-induced pathology.