KEGG   PATHWAY: pvp05416
Entry
pvp05416                    Pathway                                
Name
Viral myocarditis - Pteropus vampyrus (large flying fox)
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
pvp05416  Viral myocarditis
pvp05416

Organism
Pteropus vampyrus (large flying fox) [GN:pvp]
Gene
105290820  CXADR; coxsackievirus and adenovirus receptor isoform X1 [KO:K06788]
105309563  CD55; complement decay-accelerating factor isoform X3 [KO:K04006]
105295260  FYN; tyrosine-protein kinase Fyn [KO:K05703] [EC:2.7.10.2]
105300272  CAV1; caveolin-1 isoform X1 [KO:K06278]
105298669  ABL1; tyrosine-protein kinase ABL1 [KO:K06619] [EC:2.7.10.2]
105292845  ABL2; Abelson tyrosine-protein kinase 2 isoform X1 [KO:K08887] [EC:2.7.10.2]
105294623  RAC1; LOW QUALITY PROTEIN: ras-related C3 botulinum toxin substrate 1 [KO:K04392]
105311532  RAC2; ras-related C3 botulinum toxin substrate 2 isoform X2 [KO:K07860]
105301137  RAC3; ras-related C3 botulinum toxin substrate 3 [KO:K07861]
105294064  SSPN; sarcospan [KO:K22194]
105295407  SGCA; alpha-sarcoglycan isoform X1 [KO:K12565]
105293783  SGCB; beta-sarcoglycan isoform X1 [KO:K12566]
105293285  SGCG; gamma-sarcoglycan [KO:K12564]
105289920  SGCD; delta-sarcoglycan isoform X2 [KO:K12563]
105294327  SGCE; epsilon-sarcoglycan isoform X1 [KO:K27061]
105295568  SGCZ; zeta-sarcoglycan [KO:K27062]
105291179  LAMA2; laminin subunit alpha-2 [KO:K05637]
105296207  LAMA1; LOW QUALITY PROTEIN: laminin subunit alpha-1 [KO:K05637]
105302390  DAG1; dystroglycan [KO:K06265]
105299067  CAV3; caveolin-3 [KO:K12959]
105289401  NOS1; LOW QUALITY PROTEIN: nitric oxide synthase, brain [KO:K13240] [EC:1.14.13.39]
105304275  SNTA1; alpha-1-syntrophin [KO:K24063]
105305779  beta-2-syntrophin [KO:K24064]
105292568  SNTB1; beta-1-syntrophin [KO:K24064]
105293216  DTNA; dystrobrevin alpha isoform X2 [KO:K26998]
105304409  DMD; dystrophin isoform X1 [KO:K10366]
105301152  ACTG1; actin, cytoplasmic 2 [KO:K05692]
105294565  ACTB; actin, cytoplasmic 1 isoform X1 [KO:K05692]
105290655  EIF4G3; eukaryotic translation initiation factor 4 gamma 3 isoform X1 [KO:K03260]
105306977  EIF4G1; eukaryotic translation initiation factor 4 gamma 1 isoform X2 [KO:K03260]
105303557  EIF4G2; eukaryotic translation initiation factor 4 gamma 2 isoform X1 [KO:K03260]
105307128  uncharacterized protein LOC105307128 [KO:K04503]
105298127  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
105297238  BID; BH3-interacting domain death agonist isoform X2 [KO:K04726]
105293163  cytochrome c [KO:K08738]
105294412  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
105294710  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
105300547  myosin-6 [KO:K17751]
105300548  myosin-7 isoform X1 [KO:K17751]
105307045  CD40LG; CD40 ligand [KO:K03161]
105298191  CD40; tumor necrosis factor receptor superfamily member 5 isoform X1 [KO:K03160]
105305274  HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
105305333  DLA class II histocompatibility antigen, DR-1 beta chain [KO:K06752]
105301039  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DP beta 1 chain [KO:K06752]
105301004  LOW QUALITY PROTEIN: DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
105300960  HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752]
105300961  HLA class II histocompatibility antigen, DQ beta 1 chain isoform X1 [KO:K06752]
105300962  HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752]
105300964  HLA class II histocompatibility antigen, DO beta chain [KO:K06752]
105300969  HLA class II histocompatibility antigen, DM beta chain [KO:K06752]
105300971  HLA class II histocompatibility antigen, DM alpha chain isoform X3 [KO:K06752]
105300973  HLA class II histocompatibility antigen, DO alpha chain isoform X1 [KO:K06752]
105309227  HLA class II histocompatibility antigen, DR beta 5 chain-like [KO:K06752]
105310204  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
105310338  HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752]
105305341  HLA class I histocompatibility antigen, B-14 alpha chain-like [KO:K06751]
105293481  H-2 class I histocompatibility antigen, Q10 alpha chain-like isoform X3 [KO:K06751]
105309601  patr class I histocompatibility antigen, A-2 alpha chain-like [KO:K06751]
105309848  HLA class I histocompatibility antigen, B-38 alpha chain-like isoform X2 [KO:K06751]
105309864  HLA class I histocompatibility antigen, B-54 alpha chain-like [KO:K06751]
105310129  HLA class I histocompatibility antigen, B-40 alpha chain-like [KO:K06751]
105311725  HLA class I histocompatibility antigen, B-54 alpha chain-like [KO:K06751]
105302220  CD80; T-lymphocyte activation antigen CD80 [KO:K05412]
105288864  CD86; T-lymphocyte activation antigen CD86 [KO:K05413]
105298423  CD28; T-cell-specific surface glycoprotein CD28 isoform X1 [KO:K06470]
105300124  PRF1; perforin-1 [KO:K07818]
105304532  ITGAL; integrin alpha-L isoform X1 [KO:K05718]
105303028  ITGB2; integrin beta-2 [KO:K06464]
105305590  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
pvp03050  Proteasome
pvp04110  Cell cycle
pvp04210  Apoptosis
pvp04260  Cardiac muscle contraction
pvp04512  ECM-receptor interaction
pvp04612  Antigen processing and presentation
pvp04660  T cell receptor signaling pathway
pvp05414  Dilated cardiomyopathy
KO pathway
ko05416   
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