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 disease
PATHWAY_MAP hsa05416  Viral myocarditis
DISEASE     H00295  Viral myocarditis
ORGANISM    Homo sapiens (human) [GN:hsa]
GENE        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: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; 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]
            6444  SGCD; sarcoglycan delta [KO:K12563]
            6445  SGCG; sarcoglycan gamma [KO:K12564]
            6442  SGCA; sarcoglycan alpha [KO:K12565]
            6443  SGCB; sarcoglycan beta [KO:K12566]
            284217  LAMA1; laminin subunit alpha 1 [KO:K05637]
            3908  LAMA2; laminin subunit alpha 2 [KO:K05637]
            1605  DAG1; dystroglycan 1 [KO:K06265]
            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: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 [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]
REFERENCE   PMID:18039131
  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   PMID:12920582
  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   PMID:17200452
  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   PMID:12439638
  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   PMID:16845885
  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   PMID:16413486
  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   PMID:10904843
  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   PMID:18357777
  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   PMID:18545064
  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   PMID:19357408
  AUTHORS   Cooper LT Jr
  TITLE     Myocarditis.
  JOURNAL   N Engl J Med 360:1526-38 (2009)
            DOI:10.1056/NEJMra0800028
REFERENCE   PMID:10051305
  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   PMID:11524405
  AUTHORS   Liu PP, Mason JW
  TITLE     Advances in the understanding of myocarditis.
  JOURNAL   Circulation 104:1076-82 (2001)
            DOI:10.1161/hc3401.095198
REFERENCE   PMID:14522402
  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   PMID:16817756
  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
REL_PATHWAY 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  ko05416
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