Entry 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 diseaseBRITE hierarchy
Pathway map Ortholog table Disease 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 ]
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 ]
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 ]
637 BID; BH3 interacting domain death agonist [KO:K04726 ]
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 ]
3383 ICAM1; intercellular adhesion molecule 1 [KO:K06490 ]
Reference Authors Esfandiarei M, McManus BM
Title Molecular biology and pathogenesis of viral myocarditis.
Journal Reference Authors Badorff C, Knowlton KU
Title Dystrophin disruption in enterovirus-induced myocarditis and dilated cardiomyopathy: from bench to bedside.
Journal 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 Reference Authors Pankuweit S, Portig I, Maisch B
Title Pathophysiology of cardiac inflammation: molecular mechanisms.
Journal Reference Authors Gao G, Luo H
Title The ubiquitin-proteasome pathway in viral infections.
Journal Reference Authors Coyne CB, Bergelson JM
Title Virus-induced Abl and Fyn kinase signals permit coxsackievirus entry through epithelial tight junctions.
Journal Reference Authors Badorff C, Lee GH, Knowlton KU
Title Enteroviral cardiomyopathy: bad news for the dystrophin-glycoprotein complex.
Journal Reference Authors Knowlton KU
Title CVB infection and mechanisms of viral cardiomyopathy.
Journal Reference Authors Castellano G, Affuso F, Di Conza P, Fazio S
Title Myocarditis and dilated cardiomyopathy: possible connections and treatments.
Journal Reference Authors Cooper LT Jr
Title Myocarditis.
Journal Reference Authors Kawai C
Title From myocarditis to cardiomyopathy: mechanisms of inflammation and cell death: learning from the past for the future.
Journal Reference Authors Liu PP, Mason JW
Title Advances in the understanding of myocarditis.
Journal Reference Authors Mason JW
Title Myocarditis and dilated cardiomyopathy: an inflammatory link.
Journal Reference Authors Tam PE
Title Coxsackievirus myocarditis: interplay between virus and host in the pathogenesis of heart disease.
Journal Related hsa04612 Antigen processing and presentation
hsa04660 T cell receptor signaling pathway
KO pathway
