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

• Published in: AIDS (London) Vol. 13; no. 14; pp. 1827 - 1839
• Main Authors: Plymale, D. R., Tang, D. S., Comardelle, A. M., Fermin, C. D., Lewis, D. E., Garry, R. F.
• Format: Journal Article
• Language: English
• Published: Legacy CDMS Lippincott Williams & Wilkins 01.10.1999
• Subjects: AIDS/HIV; Apoptosis; Biological and medical sciences; Calcium; CD4 antigen; CD4-Positive T-Lymphocytes - pathology; CD4-Positive T-Lymphocytes - virology; DNA Fragmentation; Fundamental and applied biological sciences. Psychology; HIV-1 - physiology; Human immunodeficiency virus 1; Humans; Intracellular Membranes - physiology; Life Sciences (General); Microbiology; Mitochondria - physiology; Necrosis; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; Space life sciences; Tumor Cells, Cultured; U937 Cells; Virology; Virus Latency; Non-Nasa Center; Nasa Discipline Neuroscience; Immunopathology; Calcium; HIV-1 virus; Retroviridae; Cytotoxicity; AIDS; Immune deficiency; Lentivirus; Host virus relation; Necrosis; Infection; Virus; Viral disease; T-Lymphocyte; Human immunodeficiency virus; Intracellular; Mechanism of action; Fluorescence microscopy; Apoptosis; NASA Discipline Neuroscience; Non-NASA Center
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/00002030-199910010-00004

BACKGROUND: Data currently available on HIV-1-induced cytopathology is unclear 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 necrotic cells were quantified at various times after infection using video-image analysis techniques; the results were compared with the amount of fragmented DNA using a quantitative method. Measurement of mitochondrial transmembrane potential (deltapsi(m)) and intracellular calcium concentrations [Ca2+]i was performed with fluorescent probes and fluorescence concentration analysis (FCA). RESULTS: Although lymphoblastoid and monocytoid cells acutely infected by HIV-1 had increased levels of fragmented DNA, a marker of apoptotic cell death, few (<12%) had condensed chromatin and fragmented nuclei, the morphological features of apoptosis. The predominant alterations in acutely infected cells were distended endoplasmic reticulum and abnormal mitochondria; these ultrastructural changes are consistent with necrosis, although some infected cells simultaneously displayed features of both necrosis and apoptosis. Viability of cells persistently infected by HIV-1 was only minimally reduced from that of uninfected cells. This reduction was accounted for by an increased propensity of the persistently infected cells to die by apoptosis. Alterations in [Ca2+]i and deltapsi(m) occurred in both acutely and persistently infected cells. CONCLUSION: Both necrosis and apoptosis contribute to HIV-1-induced killing of CD4 cells.