PMID- 8903316
OWN - NLM
STAT- MEDLINE
DCOM- 19970103
LR  - 20181113
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 98
IP  - 9
DP  - 1996 Nov 1
TI  - Apoptosis induced by HIV-1 infection of the central nervous system.
PG  - 1979-90
AB  - 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.
FAU - Shi, B
AU  - Shi B
AD  - Division of Human Retrovirology, Dana-Farber Cancer Institute, Boston, 
      Massachusetts 02115, USA.
FAU - De Girolami, U
AU  - De Girolami U
FAU - He, J
AU  - He J
FAU - Wang, S
AU  - Wang S
FAU - Lorenzo, A
AU  - Lorenzo A
FAU - Busciglio, J
AU  - Busciglio J
FAU - Gabuzda, D
AU  - Gabuzda D
LA  - eng
GR  - NS35734/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
SB  - IM
MH  - AIDS Dementia Complex/*pathology
MH  - Adult
MH  - Aged
MH  - Alzheimer Disease/pathology
MH  - *Apoptosis
MH  - Astrocytes/microbiology/*pathology
MH  - Autopsy
MH  - Brain/embryology/microbiology
MH  - Cells, Cultured
MH  - Central Nervous System Diseases/microbiology/*pathology
MH  - DNA Fragmentation
MH  - Endothelium, Vascular/pathology
MH  - HIV Infections/*pathology
MH  - Humans
MH  - Middle Aged
MH  - Neurons/microbiology/*pathology
MH  - Time Factors
PMC - PMC507641
EDAT- 1996/11/01 00:00
MHDA- 1996/11/01 00:01
PMCR- 1996/11/01
CRDT- 1996/11/01 00:00
PHST- 1996/11/01 00:00 [pubmed]
PHST- 1996/11/01 00:01 [medline]
PHST- 1996/11/01 00:00 [entrez]
PHST- 1996/11/01 00:00 [pmc-release]
AID - 10.1172/JCI119002 [doi]
PST - ppublish
SO  - J Clin Invest. 1996 Nov 1;98(9):1979-90. doi: 10.1172/JCI119002.