INVESTIGADORES
LORENZO Alfredo Guillermo
artículos
Título:
Apoptosis induced by HIV-1 infection of the central nervous system
Autor/es:
BIN SHI; UMBERTO DE GIROLAMI; JIANGLIN HE; SHU WANG; ALFREDO LORENZO; JORGE BUSCIGLIO; DANA GABUZDA
Revista:
JOURNAL OF CLINICAL INVESTIGATION
Editorial:
AMER SOC CLINICAL INVESTIGATION INC
Referencias:
Año: 1996 vol. 98 p. 1979 - 1990
ISSN:
0021-9738
Resumen:
Apoptosis plays a role in AIDS pathogenesis in the immune
system, but its role in HIV-1?induced neurological disease is
unknown. In this study, we examine apoptosis induced by
HIV-1 infection of the central nervous system (CNS) in an
in vitro model and in brain tissue from AIDS patients. HIV-1
infection of primary brain cultures induced apoptosis in
neurons and astrocytes in vitro as determined by terminal
deoxynucleotidyl transferase-mediated dUTP nick end labeling
(TUNEL) and propidium iodide staining and by electron
microscopy. Apoptosis was not significantly induced
until 1?2 wk after the time of peak virus production, suggesting
induction by soluble factors rather than by direct viral
infection. Apoptosis of neurons and astrocytes was also
detected in brain tissue from 10/11 AIDS patients, including
5/5 patients with HIV-1 dementia and 4/5 nondemented patients.
In addition, endothelial cell apoptosis was frequently
detected in the brain of AIDS patients and was confirmed
by electron microscopy. Most of the apoptotic cells were not
localized adjacent to HIV-1?infected cells, providing further
evidence for induction by soluble factors. In six
non-AIDS control patients with normal brain, apoptotic
cells were absent or limited to rare astrocytes. However,
TUNEL-positive neurons and astrocytes were frequently
detected in seven patients with Alzheimer?s disease or abundant
senile plaques. These studies suggest that apoptosis is a
mechanism of CNS injury in AIDS which is likely to be induced
by soluble factors. The apoptosis of endothelial cells
in the CNS raises the possibility that some of these factors
may be blood-derived.