Document Detail

The 3C protease activity of enterovirus 71 induces human neural cell apoptosis.
MedLine Citation:
PMID:  11886259     Owner:  NLM     Status:  MEDLINE    
The human glioblastoma SF268 cell line was used to investigate the induction of apoptosis by the 3C protease of enterovirus 71 (EV71). Transient expression in these cells of the wild-type 3C protein encoded by EV71 induced morphological alterations typical of apoptosis, including generation of apoptotic bodies. Degradation of cellular DNA in nucleosomes was also observed. When two of the amino acids in the catalytic motif of 3C were changed by mutagenesis, the 3C protein not only lost its proteolytic activity, but also its ability to induce apoptosis in the SF268 cells. Twenty-four hours after 3C transfection, poly(ADP-ribose) polymerase, a DNA repair enzyme, was cleaved, indicating that caspases were activated by the expression of EV71 3C. The 3C-induced apoptosis was blocked by the caspase inhibitors DEVD-fmk and VAD-fmk. Our findings suggest that the proteolytic activity of 3C triggers apoptosis in the SF268 cells through a mechanism involving caspase activation and that this apoptotic pathway may play an important role in the pathogenesis of EV71 infection.
Mei-Ling Li; Tsu-An Hsu; Tzu-Chun Chen; Shih-Cheng Chang; Jin-Ching Lee; Chiann-Chyi Chen; Victor Stollar; Shin-Ru Shih
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Virology     Volume:  293     ISSN:  0042-6822     ISO Abbreviation:  Virology     Publication Date:  2002 Feb 
Date Detail:
Created Date:  2002-03-11     Completed Date:  2002-05-01     Revised Date:  2007-10-11    
Medline Journal Info:
Nlm Unique ID:  0110674     Medline TA:  Virology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  386-95     Citation Subset:  IM    
School of Medical Technology, Chang Gung University, Tao-Yuan, Taiwan.
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MeSH Terms
Amino Acid Chloromethyl Ketones / pharmacology
Apoptosis* / drug effects
Caspases / antagonists & inhibitors
Cysteine Endopeptidases / genetics,  metabolism*
Cysteine Proteinase Inhibitors / pharmacology
DNA / metabolism
Enterovirus / enzymology*,  pathogenicity
Mutagenesis, Site-Directed
Nucleosomes / pathology
Oligopeptides / pharmacology
Tumor Cells, Cultured
Viral Proteins / genetics,  metabolism*
Reg. No./Substance:
0/Amino Acid Chloromethyl Ketones; 0/Cysteine Proteinase Inhibitors; 0/Nucleosomes; 0/Oligopeptides; 0/Viral Proteins; 0/benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; 0/benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; 9007-49-2/DNA; EC 3.4.22.-/Caspases; EC 3.4.22.-/Cysteine Endopeptidases; EC proteases

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