KEGG   PATHWAY: ko05416
Entry
ko05416                     Pathway                                

Name
Viral myocarditis
Description
Myocarditis is a cardiac disease associated with inflammation and injury of the myocardium. It results from various etiologies, both noninfectious and infectious, but coxsackievirus B3 (CVB3) is still considered the dominant etiological agent. Myocarditis may be caused by direct cytopathic effects of virus, a pathologic immune response to persistent virus, or autoimmunity triggered by the viral infection. The virus enters the myocyte through internalization of the coxsackie-adenoviral receptor (CAR) and its coreceptor, decay-accelerating factor (DAF). Viral proteases cleave various proteins in the host cell. One example is viral protease 2A, which cleaves eukaryote initiation factor 4G (eIF4G) and the dystrophin protein, resulting in a complete shutdown of cap-dependent RNA translation and cytoskeletal destruction in infected cardiomyocytes, respectively. CVB3 also cleaves the member of the Bcl-2 family Bid, leading to apoptosis. CVB3 infection also induces the cleavage of cyclin D protein through a proteasome-dependent pathway, leading to the host cell-growth arrest. Viral infection and necrosis of myocytes may lead to the release of intracellular antigens, resulting in activation of self-reactive T cells. CVB infection is a significant cause of dilated cardiomyopathy (DCM) as well as myocarditis. Epidemiologically, myocarditis underlies a significant portion of patients with DCM.
Class
Human Diseases; Cardiovascular disease
Pathway map
ko05416  Viral myocarditis
ko05416

Disease
H00295  Viral myocarditis
Orthology
K06788  coxsackievirus and adenovirus receptor
K04006  decay accelerating factor
K05703  tyrosine-protein kinase Fyn [EC:2.7.10.2]
K06278  caveolin 1
K06619  abelson tyrosine-protein kinase 1 [EC:2.7.10.2]
K08887  abelson tyrosine-protein kinase 2 [EC:2.7.10.2]
K04392  Ras-related C3 botulinum toxin substrate 1
K07860  Ras-related C3 botulinum toxin substrate 2
K07861  Ras-related C3 botulinum toxin substrate 3
K12563  delta-sarcoglycan
K12564  gamma-sarcoglycan
K12565  alpha-sarcoglycan
K12566  beta-sarcoglycan
K05637  laminin, alpha 1/2
K06265  dystroglycan 1
K10366  dystrophin
K05692  actin beta/gamma 1
K03260  translation initiation factor 4G
K04503  G1/S-specific cyclin-D1
K04398  caspase 8 [EC:3.4.22.61]
K04726  BH3 interacting domain death agonist
K08738  cytochrome c
K04399  caspase 9 [EC:3.4.22.62]
K02187  caspase 3 [EC:3.4.22.56]
K17751  myosin heavy chain 6/7
K03161  tumor necrosis factor ligand superfamily member 5
K03160  tumor necrosis factor receptor superfamily member 5
K06752  MHC class II antigen
K10784  T cell receptor alpha chain V region
K10785  T-cell receptor beta chain V region
K06751  MHC class I antigen
K05412  CD80 antigen
K05413  CD86 antigen
K06470  CD28 antigen
K07818  perforin 1
K05718  integrin alpha L
K06464  integrin beta 2
K06490  intercellular adhesion molecule 1
K06856  immunoglobulin heavy chain
Reference
  Authors
Esfandiarei M, McManus BM
  Title
Molecular biology and pathogenesis of viral myocarditis.
  Journal
Annu Rev Pathol 3:127-55 (2008)
DOI:10.1146/annurev.pathmechdis.3.121806.151534
Reference
  Authors
Badorff C, Knowlton KU
  Title
Dystrophin disruption in enterovirus-induced myocarditis and dilated cardiomyopathy: from bench to bedside.
  Journal
Med Microbiol Immunol 193:121-6 (2004)
DOI:10.1007/s00430-003-0189-7
Reference
  Authors
Maekawa Y, Ouzounian M, Opavsky MA, Liu PP
  Title
Connecting the missing link between dilated cardiomyopathy and viral myocarditis: virus, cytoskeleton, and innate immunity.
  Journal
Circulation 115:5-8 (2007)
DOI:10.1161/CIRCULATIONAHA.106.670554
Reference
  Authors
Pankuweit S, Portig I, Maisch B
  Title
Pathophysiology of cardiac inflammation: molecular mechanisms.
  Journal
Herz 27:669-76 (2002)
DOI:10.1007/s00059-002-2421-4
Reference
  Authors
Gao G, Luo H
  Title
The ubiquitin-proteasome pathway in viral infections.
  Journal
Can J Physiol Pharmacol 84:5-14 (2006)
DOI:10.1139/y05-144
Reference
  Authors
Coyne CB, Bergelson JM
  Title
Virus-induced Abl and Fyn kinase signals permit coxsackievirus entry through epithelial tight junctions.
  Journal
Cell 124:119-31 (2006)
DOI:10.1016/j.cell.2005.10.035
Reference
  Authors
Badorff C, Lee GH, Knowlton KU
  Title
Enteroviral cardiomyopathy: bad news for the dystrophin-glycoprotein complex.
  Journal
Herz 25:227-32 (2000)
DOI:10.1007/s000590050011
Reference
  Authors
Knowlton KU
  Title
CVB infection and mechanisms of viral cardiomyopathy.
  Journal
Curr Top Microbiol Immunol 323:315-35 (2008)
DOI:10.1007/978-3-540-75546-3_15
Reference
  Authors
Castellano G, Affuso F, Di Conza P, Fazio S
  Title
Myocarditis and dilated cardiomyopathy: possible connections and treatments.
  Journal
J Cardiovasc Med (Hagerstown) 9:666-71 (2008)
DOI:10.2459/JCM.0b013e3282f3e9c2
Reference
  Authors
Cooper LT Jr
  Title
Myocarditis.
  Journal
N Engl J Med 360:1526-38 (2009)
DOI:10.1056/NEJMra0800028
Reference
  Authors
Kawai C
  Title
From myocarditis to cardiomyopathy: mechanisms of inflammation and cell death: learning from the past for the future.
  Journal
Circulation 99:1091-100 (1999)
DOI:10.1161/01.CIR.99.8.1091
Reference
  Authors
Liu PP, Mason JW
  Title
Advances in the understanding of myocarditis.
  Journal
Circulation 104:1076-82 (2001)
DOI:10.1161/hc3401.095198
Reference
  Authors
Mason JW
  Title
Myocarditis and dilated cardiomyopathy: an inflammatory link.
  Journal
Cardiovasc Res 60:5-10 (2003)
DOI:10.1016/S0008-6363(03)00437-1
Reference
  Authors
Tam PE
  Title
Coxsackievirus myocarditis: interplay between virus and host in the pathogenesis of heart disease.
  Journal
Viral Immunol 19:133-46 (2006)
DOI:10.1089/vim.2006.19.133
Related
pathway
ko03050  Proteasome
ko04110  Cell cycle
ko04210  Apoptosis
ko04260  Cardiac muscle contraction
ko04512  ECM-receptor interaction
ko04612  Antigen processing and presentation
ko04660  T cell receptor signaling pathway
ko05414  Dilated cardiomyopathy
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