| Coxsackievirus protein 2BC blocks host cell apoptosis by inhibiting caspase-3. | |
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MedLine Citation:
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PMID: 16608851 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Virus infection may induce host cell death by apoptosis, but some DNA viruses are capable of preventing this process. RNA viruses were thought not to display anti-apoptotic activities, as their spread appears to benefit from a rapid induction of cell death. Here, we report an antiapoptotic activity in the Picornavirus Coxsackievirus B4 (CVB4). CVB4 infection of HeLa cells induced negligible apoptosis over a period of 10 h. However, infected cells developed resistance to drug-induced apoptosis using staurosporine and actinomycin D and to death receptor-induced apoptosis using tumor necrosis factor-related apoptosis-inducing ligand. Despite this resistance, the apoptotic machinery was nonetheless fully activated in these drug-treated infected cells because the levels of pro-caspase-3 processing to its active form were similar to control cells. However, the DEVDase (Asp-Glu-Val-Asp protease) activity of the processed caspase was significantly inhibited in the virus-infected staurosporine-treated cells compared with drug treatment alone. Likewise, extracts of CVB4-infected cells suppressed recombinant caspase-3 activity in vitro. Immunoprecipitation of activated caspase-3 from radiolabeled virus-infected cells revealed the co-precipitation of a 48-kDa protein that was tentatively identified as viral protein 2BC. Recombinant caspase-3 was found to co-precipitate with virus protein 2BC. Finally, when protein 2BC was expressed in HeLa cells, both staurosporine-induced apoptosis and in vitro caspase-3 DEVDase activity were significantly reduced. Taken together these data imply that CVB4 infection suppresses apoptosis through virus protein 2BC associating with caspase-3 and inhibiting its function. Thus, 2BC is the first reported RNA virus inhibitor of apoptosis protein. |
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Authors:
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Michael A Salako; Michael J Carter; George E N Kass |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-04-11 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 281 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2006 Jun |
Date Detail:
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Created Date: 2006-06-12 Completed Date: 2006-08-01 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 16296-304 Citation Subset: IM |
Affiliation:
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School of Biomedical and Molecular Sciences, University of Surrey, Guildford, GU2 7XH, United Kingdom. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Apoptosis* Apoptosis Regulatory Proteins / metabolism Caspase 3 Caspases / antagonists & inhibitors*, metabolism Dactinomycin / pharmacology Enterovirus* Enzyme Inhibitors / pharmacology* Flow Cytometry Hela Cells Humans Membrane Glycoproteins / metabolism Molecular Sequence Data Recombinant Proteins / chemistry Sequence Homology, Amino Acid TNF-Related Apoptosis-Inducing Ligand Tumor Necrosis Factor-alpha / metabolism Viral Nonstructural Proteins / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Apoptosis Regulatory Proteins; 0/Enzyme Inhibitors; 0/Membrane Glycoproteins; 0/Recombinant Proteins; 0/TNF-Related Apoptosis-Inducing Ligand; 0/TNFSF10 protein, human; 0/Tumor Necrosis Factor-alpha; 0/Viral Nonstructural Proteins; 50-76-0/Dactinomycin; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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