KEGG   PATHWAY: mpuf05416
Entry
mpuf05416                   Pathway                                
Name
Viral myocarditis - Mustela putorius furo (domestic ferret)
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
mpuf05416  Viral myocarditis
mpuf05416

Organism
Mustela putorius furo (domestic ferret) [GN:mpuf]
Gene
101675797  CXADR; coxsackievirus and adenovirus receptor isoform X4 [KO:K06788]
101688948  CD55; complement decay-accelerating factor isoform X1 [KO:K04006]
101676005  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
101675955  CAV1; caveolin-1 isoform X1 [KO:K06278]
101689921  ABL1; tyrosine-protein kinase ABL1 [KO:K06619] [EC:2.7.10.2]
101684271  ABL2; Abelson tyrosine-protein kinase 2 isoform X1 [KO:K08887] [EC:2.7.10.2]
101693834  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
101676559  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
101688258  RAC3; ras-related C3 botulinum toxin substrate 3 [KO:K07861]
101683259  SSPN; sarcospan isoform X1 [KO:K22194]
101686508  SGCA; alpha-sarcoglycan isoform X1 [KO:K12565]
101676646  SGCB; beta-sarcoglycan [KO:K12566]
101676694  SGCG; gamma-sarcoglycan isoform X1 [KO:K12564]
101684263  SGCD; delta-sarcoglycan isoform X1 [KO:K12563]
101689363  SGCE; epsilon-sarcoglycan isoform X1 [KO:K27061]
101671937  SGCZ; zeta-sarcoglycan isoform X1 [KO:K27062]
101673993  LAMA1; laminin subunit alpha-1 [KO:K05637]
101687362  LAMA2; laminin subunit alpha-2 [KO:K05637]
101677695  DAG1; dystroglycan [KO:K06265]
101684840  CAV3; caveolin-3 [KO:K12959]
101692439  NOS1; nitric oxide synthase, brain isoform X1 [KO:K13240] [EC:1.14.13.39]
101685154  SNTA1; alpha-1-syntrophin [KO:K24063]
106003342  SNTB1; beta-1-syntrophin [KO:K24064]
101676330  beta-1-syntrophin [KO:K24064]
101676859  beta-2-syntrophin [KO:K24064]
101674122  DTNA; dystrobrevin alpha isoform X1 [KO:K26998]
101672364  DMD; dystrophin [KO:K10366]
101679540  ACTG1; actin, cytoplasmic 2 [KO:K05692]
101686268  ACTB; actin, cytoplasmic 1 [KO:K05692]
101679717  EIF4G1; eukaryotic translation initiation factor 4 gamma 1 isoform X1 [KO:K03260]
101670178  EIF4G3; eukaryotic translation initiation factor 4 gamma 3 [KO:K03260]
101683849  EIF4G2; eukaryotic translation initiation factor 4 gamma 2 [KO:K03260]
101670844  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
101678102  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
101686636  BID; BH3-interacting domain death agonist [KO:K04726]
101681070  BH3-interacting domain death agonist-like [KO:K04726]
106003371  cytochrome c, testis-specific [KO:K08738]
101690488  cytochrome c [KO:K08738]
101681290  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
101690858  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
101673577  myosin-7 [KO:K17751]
101673860  myosin-6 [KO:K17751]
101681499  CD40LG; CD40 ligand [KO:K03161]
101674384  CD40; tumor necrosis factor receptor superfamily member 5 [KO:K03160]
101691795  DLA class II histocompatibility antigen, DR-1 beta chain [KO:K06752]
101692125  RLA class II histocompatibility antigen, DP beta chain [KO:K06752]
101673877  boLa class II histocompatibility antigen, DQB*0101 beta chain-like [KO:K06752]
101674777  HLA class II histocompatibility antigen, DM beta chain isoform X1 [KO:K06752]
106003441  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DR alpha chain-like [KO:K06752]
101675687  HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752]
101682907  HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752]
101670362  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
101683191  HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752]
101683501  HLA class II histocompatibility antigen, DQ beta 2 chain-like [KO:K06752]
101677272  HLA class II histocompatibility antigen, DO alpha chain isoform X1 [KO:K06752]
101690706  HLA class II histocompatibility antigen, DO beta chain [KO:K06752]
101671551  HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
101678035  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DP alpha 1 chain [KO:K06752]
101678178  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
101684722  HLA class II histocompatibility antigen, DQ beta 2 chain-like [KO:K06752]
101690739  uncharacterized protein LOC101690739 [KO:K10784]
101686008  uncharacterized protein LOC101686008 [KO:K10785]
101693321  DLA class I histocompatibility antigen, A9/A9 alpha chain-like [KO:K06751]
101693860  HLA class I histocompatibility antigen, A-34 alpha chain-like [KO:K06751]
106004724  HLA class I histocompatibility antigen, Cw-8 alpha chain-like [KO:K06751]
101689041  HLA class I histocompatibility antigen, A-80 alpha chain-like isoform X1 [KO:K06751]
101690568  LOW QUALITY PROTEIN: DLA class I histocompatibility antigen, A9/A9 alpha chain [KO:K06751]
101673746  CD80; T-lymphocyte activation antigen CD80 [KO:K05412]
101686613  CD86; T-lymphocyte activation antigen CD86 isoform X1 [KO:K05413]
101689176  CD28; T-cell-specific surface glycoprotein CD28 isoform X1 [KO:K06470]
101688524  PRF1; perforin-1 isoform X1 [KO:K07818]
101689018  ITGAL; integrin alpha-L isoform X1 [KO:K05718]
101690974  ITGB2; integrin beta-2 [KO:K06464]
101683044  ICAM1; intercellular adhesion molecule 1 [KO:K06490]
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
mpuf03050  Proteasome
mpuf04110  Cell cycle
mpuf04210  Apoptosis
mpuf04260  Cardiac muscle contraction
mpuf04512  ECM-receptor interaction
mpuf04612  Antigen processing and presentation
mpuf04660  T cell receptor signaling pathway
mpuf05414  Dilated cardiomyopathy
KO pathway
ko05416   
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