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KEGG   PATHWAY: hsa05416
hsa05416                    Pathway                                
Viral myocarditis - Homo sapiens (human)
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
hsa05416  Viral myocarditis

H00295  Viral myocarditis
Homo sapiens (human) [GN:hsa]
1525  CXADR; CXADR Ig-like cell adhesion molecule [KO:K06788]
1604  CD55; CD55 molecule (Cromer blood group) [KO:K04006]
2534  FYN; FYN proto-oncogene, Src family tyrosine kinase [KO:K05703] [EC:]
857  CAV1; caveolin 1 [KO:K06278]
25  ABL1; ABL proto-oncogene 1, non-receptor tyrosine kinase [KO:K06619] [EC:]
27  ABL2; ABL proto-oncogene 2, non-receptor tyrosine kinase [KO:K08887] [EC:]
5879  RAC1; Rac family small GTPase 1 [KO:K04392]
5880  RAC2; Rac family small GTPase 2 [KO:K07860]
5881  RAC3; Rac family small GTPase 3 [KO:K07861]
8082  SSPN; sarcospan [KO:K22194]
6442  SGCA; sarcoglycan alpha [KO:K12565]
6443  SGCB; sarcoglycan beta [KO:K12566]
6444  SGCD; sarcoglycan delta [KO:K12563]
6445  SGCG; sarcoglycan gamma [KO:K12564]
284217  LAMA1; laminin subunit alpha 1 [KO:K05637]
3908  LAMA2; laminin subunit alpha 2 [KO:K05637]
1605  DAG1; dystroglycan 1 [KO:K06265]
859  CAV3; caveolin 3 [KO:K12959]
4842  NOS1; nitric oxide synthase 1 [KO:K13240] [EC:]
6640  SNTA1; syntrophin alpha 1 [KO:K24063]
6645  SNTB2; syntrophin beta 2 [KO:K24064]
6641  SNTB1; syntrophin beta 1 [KO:K24064]
1837  DTNA; dystrobrevin alpha [KO:K26998]
1756  DMD; dystrophin [KO:K10366]
71  ACTG1; actin gamma 1 [KO:K05692]
60  ACTB; actin beta [KO:K05692]
8672  EIF4G3; eukaryotic translation initiation factor 4 gamma 3 [KO:K03260]
1981  EIF4G1; eukaryotic translation initiation factor 4 gamma 1 [KO:K03260]
1982  EIF4G2; eukaryotic translation initiation factor 4 gamma 2 [KO:K03260]
595  CCND1; cyclin D1 [KO:K04503]
841  CASP8; caspase 8 [KO:K04398] [EC:]
637  BID; BH3 interacting domain death agonist [KO:K04726]
54205  CYCS; cytochrome c, somatic [KO:K08738]
842  CASP9; caspase 9 [KO:K04399] [EC:]
836  CASP3; caspase 3 [KO:K02187] [EC:]
4625  MYH7; myosin heavy chain 7 [KO:K17751]
4624  MYH6; myosin heavy chain 6 [KO:K17751]
959  CD40LG; CD40 ligand [KO:K03161]
958  CD40; CD40 molecule [KO:K03160]
3108  HLA-DMA; major histocompatibility complex, class II, DM alpha [KO:K06752]
3109  HLA-DMB; major histocompatibility complex, class II, DM beta [KO:K06752]
3111  HLA-DOA; major histocompatibility complex, class II, DO alpha [KO:K06752]
3112  HLA-DOB; major histocompatibility complex, class II, DO beta [KO:K06752]
3113  HLA-DPA1; major histocompatibility complex, class II, DP alpha 1 [KO:K06752]
3115  HLA-DPB1; major histocompatibility complex, class II, DP beta 1 [KO:K06752]
3117  HLA-DQA1; major histocompatibility complex, class II, DQ alpha 1 [KO:K06752]
3118  HLA-DQA2; major histocompatibility complex, class II, DQ alpha 2 [KO:K06752]
3119  HLA-DQB1; major histocompatibility complex, class II, DQ beta 1 [KO:K06752]
3122  HLA-DRA; major histocompatibility complex, class II, DR alpha [KO:K06752]
3123  HLA-DRB1; major histocompatibility complex, class II, DR beta 1 [KO:K06752]
3125  HLA-DRB3; major histocompatibility complex, class II, DR beta 3 [KO:K06752]
3126  HLA-DRB4; major histocompatibility complex, class II, DR beta 4 [KO:K06752]
3127  HLA-DRB5; major histocompatibility complex, class II, DR beta 5 [KO:K06752]
3105  HLA-A; major histocompatibility complex, class I, A [KO:K06751]
3106  HLA-B; major histocompatibility complex, class I, B [KO:K06751]
3107  HLA-C; major histocompatibility complex, class I, C [KO:K06751]
3134  HLA-F; major histocompatibility complex, class I, F [KO:K06751]
3135  HLA-G; major histocompatibility complex, class I, G [KO:K06751]
3133  HLA-E; major histocompatibility complex, class I, E [KO:K06751]
941  CD80; CD80 molecule [KO:K05412]
942  CD86; CD86 molecule [KO:K05413]
940  CD28; CD28 molecule [KO:K06470]
5551  PRF1; perforin 1 [KO:K07818]
3683  ITGAL; integrin subunit alpha L [KO:K05718]
3689  ITGB2; integrin subunit beta 2 [KO:K06464]
3383  ICAM1; intercellular adhesion molecule 1 [KO:K06490]
102723407  IGH; immunoglobulin heavy variable 4-38-2-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)
hsa03050  Proteasome
hsa04110  Cell cycle
hsa04210  Apoptosis
hsa04260  Cardiac muscle contraction
hsa04512  ECM-receptor interaction
hsa04612  Antigen processing and presentation
hsa04660  T cell receptor signaling pathway
hsa05414  Dilated cardiomyopathy
KO pathway

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