NEURAL CELL TARGETS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IN HUMAN FETAL ORGANOTYPIC CULTURES

Some children infected by HIV-1 demonstrate nervous system disease. Be cause a significant percentage of these children are believed to be in fected during gestation and it is thought that HIV-1 may infect distin ct glial populations, this work tested the hypothesis that different H IV-1 isolates can infect cells of the developing human fetal central n ervous system (CNS). Central nervous system organotypic tissue culture s derived from human fetal brain enable the study of complex interacti ons between CNS cell types. Central nervous system organotypic culture s were exposed to lymphocytotropic (L-tropic) or monocytotropic (M-tro pic) HIV-1 isolates and monitored for viral infection, HIV-1 gp41 and p24 antigens were detected by immunocytochemistry (ICC), HIV-1 RNA was localized in the cytoplasm of CNS cells by in situ hybridization (ISH ), and viral DNA was detected by polymerase chain reaction (PCR) in HI V-1-exposed cultures. Double-label ICC identified HIV-1 antigens in bo th microglia and astrocytes. These results demonstrate that both L- an d M-tropic isolates infect microglia and astrocytes in human fetal org anotypic cultures. In addition, HIV-1 infection was detected in cultur e supernatants up to day 57 postinfection and at 90 days by coculture with susceptible CEM cells, HIV-1 infection of neural cells appears to be productive. This model may permit further examination of the inter action of HIV-1 with the developing human CNS and the mechanisms of AI DS-associated neuropathology.