Both necrosis and apoptosis contribute to HIV-1-induced killing of CD4 cells

Background: Data currently available on HIV-1-induced cytopathology is uncl ear regarding the mechanism of cell killing. Objective: To clarify the extent to which apoptosis or necrosis is involved in HIV-1-induced cell death in view of conflicting existing data. Methods: T lymphoblastoid cells or peripheral blood mononuclear cells were infected by various strains of HIV-1 and the numbers of apoptotic or necrot ic cells were quantified at various times after infection using video-image analysis techniques; the results were compared with the amount of fragment ed DNA using a quantitative method. Measurement of mitochondrial transmembr ane potential (Delta Psi(m)) and intracellular calcium concentrations [Ca2](i) was performed with fluorescent probes and fluorescence concentration a nalysis (FCA). Results: Although lymphoblastoid and monocytoid cells acutely infected by H IV-1 had increased levels of fragmented DNA, a marker of apoptotic cell dea th, few (<12%) had condensed chromatin and fragmented nuclei, the morpholog ical features of apoptosis. The predominant alterations in acutely infected cells were distended endoplasmic reticulum and abnormal mitochondria; thes e ultrastructural changes are consistent with necrosis, although some infec ted cells simultaneously displayed features of both necrosis and apoptosis. Viability of cells persistently infected by HIV-1 was only minimally reduc ed from that of uninfected cells. This reduction was accounted for by an in creased propensity of the persistently infected cells to die by apoptosis. Alterations in [Ca2+](i) and Delta Psi(m) occurred in both acutely and pers istently infected cells. Conclusion: Both necrosis and apoptosis contribute to HIV-1-induced killing of CD4 cells. (C) 1999 Lippincott Williams & Wilkins.