KEGG   PATHWAY: mna05416
mna05416                    Pathway                                

Viral myocarditis - Miniopterus natalensis
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.
Human Diseases; Cardiovascular disease
Pathway map
mna05416  Viral myocarditis

Miniopterus natalensis [GN:mna]
107544706  CXADR; coxsackievirus and adenovirus receptor isoform X1 [KO:K06788]
107543131  CD55; complement decay-accelerating factor [KO:K04006]
107540684  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:]
107528537  CAV1; caveolin-1 [KO:K06278]
107524646  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:]
107531051  ABL2; Abelson tyrosine-protein kinase 2 isoform X1 [KO:K08887] [EC:]
107537599  RAC1; LOW QUALITY PROTEIN: ras-related C3 botulinum toxin substrate 1 [KO:K04392]
107545262  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
107539040  RAC3; ras-related C3 botulinum toxin substrate 3 [KO:K07861]
107537584  SGCD; delta-sarcoglycan [KO:K12563]
107526943  SGCG; gamma-sarcoglycan [KO:K12564]
107539161  SGCA; alpha-sarcoglycan [KO:K12565]
107532587  SGCB; beta-sarcoglycan [KO:K12566]
107530937  LAMA2; laminin subunit alpha-2 [KO:K05637]
107535878  LAMA1; laminin subunit alpha-1 [KO:K05637]
107529453  DAG1; dystroglycan [KO:K06265]
107539076  ACTG1; actin, cytoplasmic 2 [KO:K05692]
107537600  ACTB; actin, cytoplasmic 1 [KO:K05692]
107532296  EIF4G2; eukaryotic translation initiation factor 4 gamma 2 isoform X1 [KO:K03260]
107538374  EIF4G3; eukaryotic translation initiation factor 4 gamma 3 isoform X1 [KO:K03260]
107543120  EIF4G1; eukaryotic translation initiation factor 4 gamma 1 isoform X1 [KO:K03260]
107537434  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
107533931  CASP8; caspase-8 [KO:K04398] [EC:]
107537702  BID; LOW QUALITY PROTEIN: BH3-interacting domain death agonist [KO:K04726]
107536673  cytochrome c-like [KO:K08738]
107540285  cytochrome c isoform X1 [KO:K08738]
107533212  LOW QUALITY PROTEIN: cytochrome c-like [KO:K08738]
107531542  CASP9; caspase-9 [KO:K04399] [EC:]
107535740  CASP3; caspase-3 [KO:K02187] [EC:]
107531658  myosin-7-like [KO:K17751]
107531708  MYH6; myosin-6 isoform X1 [KO:K17751]
107539933  CD40LG; CD40 ligand [KO:K03161]
107530873  CD40; tumor necrosis factor receptor superfamily member 5 isoform X1 [KO:K03160]
107545174  HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752]
107536419  DLA class II histocompatibility antigen, DR-1 beta chain [KO:K06752]
107544122  HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
107542667  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DP beta 1 chain [KO:K06752]
107542672  HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752]
107542674  HLA class II histocompatibility antigen, DM beta chain [KO:K06752]
107545091  HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752]
107545092  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
107531685  uncharacterized protein LOC107531685 [KO:K10784]
107538488  patr class I histocompatibility antigen, A-2 alpha chain-like [KO:K06751]
107538961  saoe class I histocompatibility antigen, A alpha chain-like [KO:K06751]
107525813  saoe class I histocompatibility antigen, A alpha chain-like [KO:K06751]
107546126  LOW QUALITY PROTEIN: BOLA class I histocompatibility antigen, alpha chain BL3-6-like [KO:K06751]
107546127  class I histocompatibility antigen, Gogo-C*0101/C*0102 alpha chain-like [KO:K06751]
107528441  H-2 class I histocompatibility antigen, Q10 alpha chain-like isoform X1 [KO:K06751]
107527336  CD80; T-lymphocyte activation antigen CD80 [KO:K05412]
107527343  CD86; T-lymphocyte activation antigen CD86 [KO:K05413]
107524832  CD28; T-cell-specific surface glycoprotein CD28 [KO:K06470]
107526074  PRF1; perforin-1 [KO:K07818]
107541988  ITGAL; integrin alpha-L [KO:K05718]
107543669  ITGB2; integrin beta-2 [KO:K06464]
107533247  ICAM1; intercellular adhesion molecule 1 [KO:K06490]
Esfandiarei M, McManus BM
Molecular biology and pathogenesis of viral myocarditis.
Annu Rev Pathol 3:127-55 (2008)
Badorff C, Knowlton KU
Dystrophin disruption in enterovirus-induced myocarditis and dilated cardiomyopathy: from bench to bedside.
Med Microbiol Immunol 193:121-6 (2004)
Maekawa Y, Ouzounian M, Opavsky MA, Liu PP
Connecting the missing link between dilated cardiomyopathy and viral myocarditis: virus, cytoskeleton, and innate immunity.
Circulation 115:5-8 (2007)
Pankuweit S, Portig I, Maisch B
Pathophysiology of cardiac inflammation: molecular mechanisms.
Herz 27:669-76 (2002)
Gao G, Luo H
The ubiquitin-proteasome pathway in viral infections.
Can J Physiol Pharmacol 84:5-14 (2006)
Coyne CB, Bergelson JM
Virus-induced Abl and Fyn kinase signals permit coxsackievirus entry through epithelial tight junctions.
Cell 124:119-31 (2006)
Badorff C, Lee GH, Knowlton KU
Enteroviral cardiomyopathy: bad news for the dystrophin-glycoprotein complex.
Herz 25:227-32 (2000)
Knowlton KU
CVB infection and mechanisms of viral cardiomyopathy.
Curr Top Microbiol Immunol 323:315-35 (2008)
Castellano G, Affuso F, Di Conza P, Fazio S
Myocarditis and dilated cardiomyopathy: possible connections and treatments.
J Cardiovasc Med (Hagerstown) 9:666-71 (2008)
Cooper LT Jr
N Engl J Med 360:1526-38 (2009)
Kawai C
From myocarditis to cardiomyopathy: mechanisms of inflammation and cell death: learning from the past for the future.
Circulation 99:1091-100 (1999)
Liu PP, Mason JW
Advances in the understanding of myocarditis.
Circulation 104:1076-82 (2001)
Mason JW
Myocarditis and dilated cardiomyopathy: an inflammatory link.
Cardiovasc Res 60:5-10 (2003)
Tam PE
Coxsackievirus myocarditis: interplay between virus and host in the pathogenesis of heart disease.
Viral Immunol 19:133-46 (2006)
mna03050  Proteasome
mna04110  Cell cycle
mna04210  Apoptosis
mna04260  Cardiac muscle contraction
mna04512  ECM-receptor interaction
mna04612  Antigen processing and presentation
mna04660  T cell receptor signaling pathway
mna05414  Dilated cardiomyopathy
KO pathway

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