title: Proteomic analysis reveals virus-specific Hsp25 modulation in cardiac myocytes.
abstract: Viruses frequently infect the heart but clinical myocarditis is rare, suggesting that the cardiac antiviral response is uniquely effective. Indeed, the Type I interferon (IFN) response is cardiac cell-type specific and provides one integrated network of protection for the heart. Here, a proteomic approach was used to identify additional proteins that may be involved in the cardiac antiviral response. Reovirus-induced murine myocarditis reflects direct viral damage to cardiac cells and offers an excellent system for study. Primary cultures of murine cardiac myocytes were infected with myocarditic or nonmyocarditic reovirus strains, and whole cell lysates were compared by two-dimensional difference gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF/TOF) tandem mass spectrometry. Results were quantitative and reproducible and demonstrated that whole proteome changes clustered according to viral pathogenic phenotype. Moreover, the data suggest that the heat shock protein Hsp25 is modulated differentially by myocarditic and nonmyocarditic reoviruses and may play a role in the cardiac antiviral response. Members of seven virus families modulate Hsp25 or Hsp27 expression in a variety of cell types, suggesting that Hsp25 participation in the antiviral response may be widespread. However, results here provide the first evidence for a virus-induced decrease in Hsp25/27 and suggest that viruses may have evolved a mechanism to subvert this protective response, as they have for IFN.
authors.affiliation: Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, North Carolina 27606, USA.
authors.forename: Lianna
authors.initials: L
authors.lastname: Li
authors.forename: Joel R
authors.initials: JR
authors.lastname: Sevinsky
authors.forename: Megan D
authors.initials: MD
authors.lastname: Rowland
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Bundy
authors.forename: James L
authors.initials: JL
authors.lastname: Stephenson
authors.forename: Barbara
authors.initials: B
authors.lastname: Sherry
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D005347:Fibroblasts / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism*; D007372:Interferons / Q000378:metabolism; D051379:Mice; D018832:Molecular Chaperones; D009205:Myocarditis / Q000378:metabolism / Q000821:virology; D009206:Myocardium / Q000166:cytology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000821:virology*; D009363:Neoplasm Proteins / Q000378:metabolism*; D030102:Orthoreovirus, Mammalian; D010766:Phosphorylation; D025341:Principal Component Analysis; D040901:Proteomics / Q000379:methods*; D012088:Reoviridae Infections / Q000378:metabolism / Q000821:virology; D015203:Reproducibility of Results; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D006360:Heat-Shock Proteins; C486113:Hsbp1 protein, mouse; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D007372:Interferons; D048051:p38 Mitogen-Activated Protein Kinases