Document Detail


JC virus induces nonapoptotic cell death of human central nervous system progenitor cell-derived astrocytes.
MedLine Citation:
PMID:  15078969     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
JC virus (JCV), a human neurotropic polyomavirus, demonstrates a selective glial cell tropism that causes cell death through lytic infection. Whether these cells die via apoptosis or necrosis following infection with JCV remains unclear. To investigate the mechanism of virus-induced cell death, we used a human central nervous system progenitor-derived astrocyte cell culture model developed in our laboratory. Using in situ DNA hybridization, immunocytochemistry, electron microscopy, and an RNase protection assay, we observed that astrocytes support a progressive JCV infection, which eventually leads to nonapoptotic cell death. Infected astrocyte cell cultures showed no difference from noninfected cells in mRNA expression of the caspase family genes or in any ultrastructural features associated with apoptosis. Infected cells demonstrated striking necrotic features such as cytoplasmic vacuolization, watery cytoplasm, and dissolution of organelles. Furthermore, staining for caspase-3 and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling were not detected in infected astrocyte cultures. Our findings suggest that JCV-induced cell death of these progenitor cell-derived astrocytes does not utilize an apoptosis pathway but exhibits a pattern of cell destruction consistent with necrotic cell death.
Authors:
Pankaj Seth; Frank Diaz; Jung-Hwa Tao-Cheng; Eugene O Major
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of virology     Volume:  78     ISSN:  0022-538X     ISO Abbreviation:  J. Virol.     Publication Date:  2004 May 
Date Detail:
Created Date:  2004-04-13     Completed Date:  2004-06-01     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4884-91     Citation Subset:  IM    
Affiliation:
Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
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MeSH Terms
Descriptor/Qualifier:
Astrocytes / pathology*,  virology*
Cell Death
Central Nervous System / cytology
Humans
In Situ Nick-End Labeling
JC Virus / genetics,  pathogenicity*,  physiology
Microscopy, Electron
Necrosis
Stem Cells / cytology
Viral Structural Proteins / genetics,  metabolism
Virion / metabolism,  ultrastructure
Virus Replication
Chemical
Reg. No./Substance:
0/Viral Structural Proteins
Comments/Corrections

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