HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1-INFECTED MONOCYTIC CELLS CAN DESTROY HUMAN NEURAL CELLS AFTER CELL-TO-CELL ADHESION

Primary cultures of human embryonic neurons and astrocytes have been used to test the interactions between neural cells and either human immunodeficiency virus type 1 (HIV-1) or HIV-1-infected monocytes. After direct infection with HIV-1, neither morphological alteration of neurons and astrocytes nor signs of viral replication were observed. Similarly, cultured human neurons and astrocytes were resistant to incubation with the supernatant of HIV-1-infected U937 cells, a human monoblastoid cell line. In contrast, HIV-1-infected U937 monocytic cells adhered to neural cells and induced large plaques of necrosis surrounding them. This cytopathic effect began at the time of viral replication (day 16 after infection). Its intensity depended on that of viral replication, and its range was identical to the region of diffusion of viral antigens, as judged by immunocytochemistry. The cytopathic effect was not dependent on the release of free radicals. It could not be induced by cytokines or cytokine-stimulated U937 cells. It is likely that this cytopathic effect depends on the release of viral antigens either within the site of adherence itself or within close range of the astrocyte membrane.