Document Detail


A proapoptotic peptide derived from reovirus outer capsid protein {micro}1 has membrane-destabilizing activity.
MedLine Citation:
PMID:  21106751     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The reovirus outer capsid protein μ1 is responsible for cell membrane penetration during virus entry and contains determinants necessary for virus-induced apoptosis. Residues 582 to 611 of μ1 are necessary and sufficient for reovirus-induced apoptosis, and residues 594 and 595 independently regulate the efficiency of viral entry and reovirus-induced cell apoptosis, respectively. Two of three α-helices within this region, helix 1 (residues 582 to 611) and helix 3 (residues 644 to 675), play a role in reovirus-induced apoptosis. Here, we chemically synthesized peptides representing helix 1 (H1), H1:K594D, H1:I595K, and helix 3 (H3) and examined their biological properties. We found that H1, but not H3, was able to cause concentration- and size-dependent leakage of molecules from small unilamellar liposomes. We further found that direct application of H1, but not H1:K594D, H1:I595K, or H3, to cells resulted in cytotoxicity. Application of the H1 peptide to L929 cells caused rapid elevations in intracellular calcium concentration that were independent of phospholipase C activation. Cytotoxicity of H1 was not restricted to eukaryotic cells, as the H1 peptide also had bactericidal activity. Based on these findings, we propose that the proapoptotic function of the H1 region of μ1 is dependent on its capacity to destabilize cellular membranes and cause release of molecules from intracellular organelles that ultimately induces cell necrosis or apoptosis, depending on the dose.
Authors:
Jae-Won Kim; Sangbom M Lyi; Colin R Parrish; John S L Parker
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-11-24
Journal Detail:
Title:  Journal of virology     Volume:  85     ISSN:  1098-5514     ISO Abbreviation:  J. Virol.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-21     Completed Date:  2011-03-07     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1507-16     Citation Subset:  IM    
Affiliation:
Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Hungerford Hill Road, Ithaca, New York 14853, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Apoptosis / drug effects*
CHO Cells
Capsid Proteins / chemistry*,  genetics,  metabolism
Cell Membrane / drug effects*,  virology
Cell Membrane Permeability
Circular Dichroism
Cricetinae
Cricetulus
Erythrocytes / physiology
Hemolysis
L Cells (Cell Line)
Liposomes / metabolism
Mice
Models, Molecular
Molecular Sequence Data
Orthoreovirus, Mammalian / genetics,  pathogenicity*,  physiology
Peptides / chemical synthesis,  chemistry*,  genetics,  pharmacology
Grant Support
ID/Acronym/Agency:
R01 AI063036/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Capsid Proteins; 0/Liposomes; 0/Peptides; 0/mu1 protein, Reovirus
Comments/Corrections

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