HUMAN-IMMUNODEFICIENCY-VIRUS - INDUCED CELL-DEATH IN CYTOKINE-TREATEDMACROPHAGES CAN BE PREVENTED BY COMPOUNDS THAT INHIBIT LATE STAGES OFVIRAL REPLICATION

The basis of the cytopathic effect induced by a laboratory strain and several clinical isolates of human immunodeficiency virus (HIV) in hum an macrophages cultured in the presence of macrophage colony-stimulati ng factor was studied. Infected macrophages die of necrosis, the conse quence of the production of mature virions in infected cells. Cell dea th can be prevented by antiviral compounds that interfere with the ass embly and budding of virions. Programmed cell death (apoptosis), a pot ential mechanism of HIV-mediated cell death in CD4 T lymphocytes, does not occur in infected macrophages as shown by electron microscopy, cy tofluorometric and gel electrophoretic DNA analysis, and nuclear fluor escent staining by Hoechst and terminal dUTP-nick-end-labeling (TUNEL) assay. The data suggest that macrophage killing by HIV may occur in v ivo. Thus, combination therapies that include compounds that inhibit t he cytopathic effect of HIV in macrophages should be considered for AI DS patients.