KEGG   PATHWAY: ray05416
ray05416                    Pathway                                

Viral myocarditis - Rousettus aegyptiacus (Egyptian rousette)
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
ray05416  Viral myocarditis

Rousettus aegyptiacus (Egyptian rousette) [GN:ray]
107512689  CXADR; coxsackievirus and adenovirus receptor [KO:K06788]
107497815  CD55; LOW QUALITY PROTEIN: complement decay-accelerating factor [KO:K04006]
107506307  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:]
107497470  CAV1; caveolin-1 isoform X1 [KO:K06278]
107504550  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:]
107509025  ABL2; Abelson tyrosine-protein kinase 2 isoform X1 [KO:K08887] [EC:]
107515925  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
107519267  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
107520254  RAC3; ras-related C3 botulinum toxin substrate 3 [KO:K07861]
107521917  SGCD; delta-sarcoglycan [KO:K12563]
107507608  gamma-sarcoglycan-like isoform X1 [KO:K12564]
107519710  SGCG; gamma-sarcoglycan [KO:K12564]
107517617  SGCA; alpha-sarcoglycan [KO:K12565]
107513944  SGCB; LOW QUALITY PROTEIN: beta-sarcoglycan [KO:K12566]
107497012  LAMA2; laminin subunit alpha-2 [KO:K05637]
107498184  LAMA1; LOW QUALITY PROTEIN: laminin subunit alpha-1 [KO:K05637]
107513352  DAG1; dystroglycan [KO:K06265]
107520262  ACTG1; actin, cytoplasmic 2 [KO:K05692]
107515934  ACTB; actin, cytoplasmic 1 [KO:K05692]
107512124  EIF4G2; eukaryotic translation initiation factor 4 gamma 2 [KO:K03260]
107504912  EIF4G1; LOW QUALITY PROTEIN: eukaryotic translation initiation factor 4 gamma 1 [KO:K03260]
107513047  EIF4G3; eukaryotic translation initiation factor 4 gamma 3 isoform X1 [KO:K03260]
107503391  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
107503155  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:]
107500447  BID; BH3-interacting domain death agonist isoform X1 [KO:K04726]
107518128  cytochrome c [KO:K08738]
107501830  CASP9; caspase-9 [KO:K04399] [EC:]
107510456  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:]
107498010  MYH6; myosin-6 [KO:K17751]
107498011  myosin-7 [KO:K17751]
107501399  CD40LG; CD40 ligand [KO:K03161]
107514532  CD40; tumor necrosis factor receptor superfamily member 5 isoform X1 [KO:K03160]
107506765  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
107506766  HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
107505772  HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752]
107505773  boLa class II histocompatibility antigen, DQB*0101 beta chain-like [KO:K06752]
107505774  HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752]
107511941  H-2 class II histocompatibility antigen, A-R alpha chain-like [KO:K06752]
107511990  HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
107511992  HLA class II histocompatibility antigen, DM beta chain [KO:K06752]
107511993  HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752]
107511999  HLA class II histocompatibility antigen, DO beta chain isoform X1 [KO:K06752]
107512001  HLA class II histocompatibility antigen, DQ beta 1 chain-like isoform X1 [KO:K06752]
107507331  HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752]
107507332  SLA class II histocompatibility antigen, DQ haplotype C beta chain-like isoform X1 [KO:K06752]
107516945  uncharacterized protein LOC107516945 [KO:K10785]
107505290  saoe class I histocompatibility antigen, A alpha chain-like [KO:K06751]
107503252  HLA class I histocompatibility antigen, B-48 alpha chain-like isoform X1 [KO:K06751]
107517540  H-2 class I histocompatibility antigen, Q10 alpha chain-like isoform X1 [KO:K06751]
107519335  LOW QUALITY PROTEIN: HLA class I histocompatibility antigen, B-46 alpha chain-like [KO:K06751]
107506412  HLA class I histocompatibility antigen, A-30 alpha chain-like [KO:K06751]
107506470  patr class I histocompatibility antigen, B-2 alpha chain-like isoform X1 [KO:K06751]
107506555  patr class I histocompatibility antigen, A-126 alpha chain-like isoform X1 [KO:K06751]
107509876  HLA class I histocompatibility antigen, B-48 alpha chain-like [KO:K06751]
107511741  saoe class I histocompatibility antigen, A alpha chain-like [KO:K06751]
107520746  HLA class I histocompatibility antigen, A-30 alpha chain-like isoform X1 [KO:K06751]
107521730  HLA class I histocompatibility antigen, B-15 alpha chain-like [KO:K06751]
107507129  HLA class I histocompatibility antigen, B-14 alpha chain-like isoform X1 [KO:K06751]
107506218  HLA class I histocompatibility antigen, B-14 alpha chain-like isoform X1 [KO:K06751]
107498449  HLA class I histocompatibility antigen, B-15 alpha chain-like isoform X1 [KO:K06751]
107508366  CD80; T-lymphocyte activation antigen CD80 [KO:K05412]
107497773  CD86; T-lymphocyte activation antigen CD86 isoform X1 [KO:K05413]
107519371  CD28; T-cell-specific surface glycoprotein CD28 isoform X1 [KO:K06470]
107498223  PRF1; perforin-1 [KO:K07818]
107515868  ITGAL; integrin alpha-L isoform X1 [KO:K05718]
107510212  ITGB2; integrin beta-2 isoform X1 [KO:K06464]
107515099  ICAM1; intercellular adhesion molecule 1 isoform X1 [KO:K06490]
107507577  Ig heavy chain Mem5-like [KO:K06856]
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)
ray03050  Proteasome
ray04110  Cell cycle
ray04210  Apoptosis
ray04260  Cardiac muscle contraction
ray04512  ECM-receptor interaction
ray04612  Antigen processing and presentation
ray04660  T cell receptor signaling pathway
ray05414  Dilated cardiomyopathy
KO pathway

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