KEGG   PATHWAY: hsa05416Help
Entry
hsa05416                    Pathway                                

Name
Viral myocarditis - Homo sapiens (human)
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 diseases
BRITE hierarchy
Pathway map
Viral myocarditis
hsa05416

All organismsOrtholog table
Disease
H00295  
Viral myocarditis
Organism
Homo sapiens (human) [GN:hsa]
Gene
1525  
CXADR; coxsackie virus and adenovirus receptor [KO:K06788]
1604  
CD55; CD55 molecule (Cromer blood group) [KO:K04006]
2534  
FYN; FYN proto-oncogene, Src family tyrosine kinase [KO:K05703] [EC:2.7.10.2]
857  
CAV1; caveolin 1 [KO:K06278]
25  
ABL1; ABL proto-oncogene 1, non-receptor tyrosine kinase [KO:K06619] [EC:2.7.10.2]
27  
ABL2; ABL proto-oncogene 2, non-receptor tyrosine kinase [KO:K08887] [EC:2.7.10.2]
5879  
RAC1; ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) [KO:K04392]
5880  
RAC2; ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2) [KO:K07860]
5881  
RAC3; ras-related C3 botulinum toxin substrate 3 (rho family, small GTP binding protein Rac3) [KO:K07861]
6444  
SGCD; sarcoglycan delta [KO:K12563]
6445  
SGCG; sarcoglycan gamma [KO:K12564]
6442  
SGCA; sarcoglycan alpha [KO:K12565]
6443  
SGCB; sarcoglycan beta [KO:K12566]
1605  
DAG1; dystroglycan 1 [KO:K06265]
1756  
DMD; dystrophin [KO:K10366]
60  
ACTB; actin, beta [KO:K05692]
71  
ACTG1; actin gamma 1 [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:3.4.22.61]
637  
BID; BH3 interacting domain death agonist [KO:K04726]
54205  
CYCS; cytochrome c, somatic [KO:K08738]
842  
CASP9; caspase 9 [KO:K04399] [EC:3.4.22.62]
836  
CASP3; caspase 3 [KO:K02187] [EC:3.4.22.56]
4625  
MYH7; myosin, heavy chain 7, cardiac muscle, beta [KO:K17751]
4624  
MYH6; myosin, heavy chain 6, cardiac muscle, alpha [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]
HLA-DRB1; HLA class II histocompatibility antigen, DRB1-7 beta chain [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]
putative V-set and immunoglobulin domain-containing-like protein IGHV4OR15-8; K06856 immunoglobulin heavy chain [KO:K06856]
3908  
LAMA2; laminin subunit alpha 2 [KO:K05637]
Reference
  Authors
Esfandiarei M, McManus BM
  Title
Molecular biology and pathogenesis of viral myocarditis.
  Journal
Annu Rev Pathol 3:127-55 (2008)
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)
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)
Reference
  Authors
Pankuweit S, Portig I, Maisch B
  Title
Pathophysiology of cardiac inflammation: molecular mechanisms.
  Journal
Herz 27:669-76 (2002)
Reference
  Authors
Gao G, Luo H
  Title
The ubiquitin-proteasome pathway in viral infections.
  Journal
Can J Physiol Pharmacol 84:5-14 (2006)
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)
Reference
  Authors
Badorff C, Lee GH, Knowlton KU
  Title
Enteroviral cardiomyopathy: bad news for the dystrophin-glycoprotein complex.
  Journal
Herz 25:227-32 (2000)
Reference
  Authors
Knowlton KU
  Title
CVB infection and mechanisms of viral cardiomyopathy.
  Journal
Curr Top Microbiol Immunol 323:315-35 (2008)
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)
Reference
  Authors
Cooper LT Jr
  Title
Myocarditis.
  Journal
N Engl J Med 360:1526-38 (2009)
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)
Reference
  Authors
Liu PP, Mason JW
  Title
Advances in the understanding of myocarditis.
  Journal
Circulation 104:1076-82 (2001)
Reference
  Authors
Mason JW
  Title
Myocarditis and dilated cardiomyopathy: an inflammatory link.
  Journal
Cardiovasc Res 60:5-10 (2003)
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)
KO pathway
 

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