KEGG PATHWAY: hsa05416

PATHWAY: hsa05416

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

Pathway map

hsa05416

Viral myocarditis

Disease

H00295

Viral myocarditis

Organism

Homo sapiens (human) [GN:hsa]

Gene

1525	CXADR; coxsackie virus and adenovirus receptor [KO:K06788]
1604	CD55; CD55 molecule, decay accelerating factor for complement (Cromer blood group) [KO:K04006]
2534	FYN; FYN oncogene related to SRC, FGR, YES [KO:K05703] [EC:2.7.10.2]
857	CAV1; caveolin 1, caveolae protein, 22kDa [KO:K06278]
25	ABL1; c-abl oncogene 1, non-receptor tyrosine kinase [KO:K06619] [EC:2.7.10.2]
27	ABL2; v-abl Abelson murine leukemia viral oncogene homolog 2 [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 (35kDa dystrophin-associated glycoprotein) [KO:K12563]
6445	SGCG; sarcoglycan, gamma (35kDa dystrophin-associated glycoprotein) [KO:K12564]
6442	SGCA; sarcoglycan, alpha (50kDa dystrophin-associated glycoprotein) [KO:K12565]
6443	SGCB; sarcoglycan, beta (43kDa dystrophin-associated glycoprotein) [KO:K12566]
1605	DAG1; dystroglycan 1 (dystrophin-associated glycoprotein 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, apoptosis-related cysteine peptidase [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, apoptosis-related cysteine peptidase [KO:K04399] [EC:3.4.22.62]
836	CASP3; caspase 3, apoptosis-related cysteine peptidase [KO:K02187] [EC:3.4.22.56]
22989	MYH15; myosin, heavy chain 15 [KO:K10352]
4619	MYH1; myosin, heavy chain 1, skeletal muscle, adult [KO:K10352]
4620	MYH2; myosin, heavy chain 2, skeletal muscle, adult [KO:K10352]
4621	MYH3; myosin, heavy chain 3, skeletal muscle, embryonic [KO:K10352]
4622	MYH4; myosin, heavy chain 4, skeletal muscle [KO:K10352]
4624	MYH6; myosin, heavy chain 6, cardiac muscle, alpha [KO:K10352]
4625	MYH7; myosin, heavy chain 7, cardiac muscle, beta [KO:K10352]
4626	MYH8; myosin, heavy chain 8, skeletal muscle, perinatal [KO:K10352]
4627	MYH9; myosin, heavy chain 9, non-muscle [KO:K10352]
4628	MYH10; myosin, heavy chain 10, non-muscle [KO:K10352]
4629	MYH11; myosin, heavy chain 11, smooth muscle [KO:K10352]
57644	MYH7B; myosin, heavy chain 7B, cardiac muscle, beta [KO:K10352]
79784	MYH14; myosin, heavy chain 14, non-muscle [KO:K10352]
8735	MYH13; myosin, heavy chain 13, skeletal muscle [KO:K10352]
959	CD40LG; CD40 ligand [KO:K03161]
958	CD40; CD40 molecule, TNF receptor superfamily member 5 [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]
100507709	HLA class II histocompatibility antigen; K06752 major histocompatibility complex, class II [KO:K06752]
100507714	HLA class II histocompatibility antigen; K06752 major histocompatibility complex, class II [KO:K06752]
100509457	HLA class II histocompatibility antigen; K06752 major histocompatibility complex, class II [KO:K06752]
101060835	HLA class II histocompatibility antigen; K06752 major histocompatibility complex, class II [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 (pore forming protein) [KO:K07818]
3683	ITGAL; integrin, alpha L (antigen CD11A (p180), lymphocyte function-associated antigen 1 [KO:K05718]
3689	ITGB2; integrin, beta 2 (complement component 3 receptor 3 and 4 subunit) [KO:K06464]
3383	ICAM1; intercellular adhesion molecule 1 [KO:K06490]
3908	LAMA2; laminin, alpha 2 [KO:K05637]

Reference

PMID:18039131

Authors

Esfandiarei M, McManus BM

Title

Molecular biology and pathogenesis of viral myocarditis.

Journal

Annu Rev Pathol 3:127-55 (2008)

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)

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)

Reference

PMID:12439638

Authors

Pankuweit S, Portig I, Maisch B

Title

Pathophysiology of cardiac inflammation: molecular mechanisms.

Journal

Herz 27:669-76 (2002)

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)

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)

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)

Reference

PMID:18357777

Authors

Knowlton KU

Title

CVB infection and mechanisms of viral cardiomyopathy.

Journal

Curr Top Microbiol Immunol 323:315-35 (2008)

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)

Reference

PMID:19357408

Authors

Cooper LT Jr

Title

Myocarditis.

Journal

N Engl J Med 360:1526-38 (2009)

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)

Reference

PMID:11524405

Authors

Liu PP, Mason JW

Title

Advances in the understanding of myocarditis.

Journal

Circulation 104:1076-82 (2001)

Reference

PMID:14522402

Authors

Mason JW

Title

Myocarditis and dilated cardiomyopathy: an inflammatory link.

Journal

Cardiovasc Res 60:5-10 (2003)

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)

KO pathway

ko05416

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Ontology (3)   
   KEGG BRITE (3)   
Pathway (1)   
   BioSystems (1)   
Disease (1)   
   KEGG DISEASE (1)   
Genome (1)   
   KEGG GENOME (1)   
Gene (74)   
   KEGG GENES (74)   
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