Document Detail


Reovirus infection or ectopic expression of outer capsid protein micro1 induces apoptosis independently of the cellular proapoptotic proteins Bax and Bak.
MedLine Citation:
PMID:  20980509     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mammalian orthoreoviruses induce apoptosis in vivo and in vitro; however, the specific mechanism by which apoptosis is induced is not fully understood. Recent studies have indicated that the reovirus outer capsid protein μ1 is the primary determinant of reovirus-induced apoptosis. Ectopically expressed μ1 induces apoptosis and localizes to intracellular membranes. Here we report that ectopic expression of μ1 activated both the extrinsic and intrinsic apoptotic pathways with activation of initiator caspases-8 and -9 and downstream effector caspase-3. Activation of both pathways was required for μ1-induced apoptosis, as specific inhibition of either caspase-8 or caspase-9 abolished downstream effector caspase-3 activation. Similar to reovirus infection, ectopic expression of μ1 caused release into the cytosol of cytochrome c and smac/DIABLO from the mitochondrial intermembrane space. Pancaspase inhibitors did not prevent cytochrome c release from cells expressing μ1, indicating that caspases were not required. Additionally, μ1- or reovirus-induced release of cytochrome c occurred efficiently in Bax(-/-)Bak(-/-) mouse embryonic fibroblasts (MEFs). Finally, we found that reovirus-induced apoptosis occurred in Bax(-/-)Bak(-/-) MEFs, indicating that reovirus-induced apoptosis occurs independently of the proapoptotic Bcl-2 family members Bax and Bak.
Authors:
Meagan L Wisniewski; Brenda G Werner; Louis G Hom; Lynne J Anguish; Caroline M Coffey; John S L Parker
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-10-27
Journal Detail:
Title:  Journal of virology     Volume:  85     ISSN:  1098-5514     ISO Abbreviation:  J. Virol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-14     Completed Date:  2011-01-20     Revised Date:  2011-08-01    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  296-304     Citation Subset:  IM    
Affiliation:
Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Hungerford Hill Road, Ithaca, NY 14853, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / physiology*
CHO Cells
Capsid Proteins / genetics,  metabolism*,  pharmacology
Carrier Proteins / genetics,  metabolism
Caspases / genetics,  metabolism
Cell Line
Cricetinae
Cricetulus
Cytochromes c / genetics,  metabolism
Cytosol / metabolism
Fibroblasts / virology
Hela Cells
Humans
Intracellular Membranes / metabolism
Mammalian orthoreovirus 3 / pathogenicity*
Mice
Mitochondria / metabolism
Mitochondrial Proteins / genetics,  metabolism
Orthoreovirus, Mammalian / pathogenicity*
bcl-2 Homologous Antagonist-Killer Protein / genetics,  metabolism*
bcl-2-Associated X Protein / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
R01 AI063036/AI/NIAID NIH HHS; T32 AI07618/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Capsid Proteins; 0/Carrier Proteins; 0/Mitochondrial Proteins; 0/bcl-2 Homologous Antagonist-Killer Protein; 0/bcl-2-Associated X Protein; 9007-43-6/Cytochromes c; EC 3.4.22.-/Caspases
Comments/Corrections

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