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


CONCLUSIONS
Both necrosis and apoptosis contribute to HIV-1-induced killing of CD4 cells.
Plymale
D R
DR
Interdisciplinary Graduate Program in Molecular and Cellular Biology, Tulane University, New Orleans, Louisiana 70112, USA.
Tang
D S
DS
Comardelle
A M
AM
Fermin
C D
CD
Lewis
D E
DE
Garry
R F
RF
D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology* / Q000821:virology; D002118:Calcium; D053938:DNA Fragmentation; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007425:Intracellular Membranes / Q000502:physiology; D008928:Mitochondria / Q000502:physiology; D009336:Necrosis; D014407:Tumor Cells, Cultured; D020298:U937 Cells; D017735:Virus Latency
D002118:Calcium