Entry Name Viral myocarditis - Phascolarctos cinereus (koala)
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 Organism Phascolarctos cinereus (koala) [GN:
pcw ]
Gene 110219629 CD55; complement decay-accelerating factor isoform X1 [KO:K04006 ]
110193513 RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392 ]
110218260 RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861 ]
110221204 EIF4G1; eukaryotic translation initiation factor 4 gamma 1 isoform X1 [KO:K03260 ]
110198726 EIF4G3; eukaryotic translation initiation factor 4 gamma 3 isoform X1 [KO:K03260 ]
110218912 EIF4G2; eukaryotic translation initiation factor 4 gamma 2 [KO:K03260 ]
110193707 CD40; tumor necrosis factor receptor superfamily member 5 isoform X1 [KO:K03160 ]
110203296 DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752 ]
110201282 H-2 class II histocompatibility antigen, E-S beta chain-like [KO:K06752 ]
110204537 DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752 ]
110199338 rano class II histocompatibility antigen, A beta chain-like isoform X1 [KO:K06752 ]
110199339 HLA class II histocompatibility antigen, DQ beta 2 chain-like [KO:K06752 ]
110199388 H-2 class II histocompatibility antigen, A-R alpha chain-like [KO:K06752 ]
110199389 mamu class II histocompatibility antigen, DR alpha chain-like [KO:K06752 ]
110199403 rano class II histocompatibility antigen, A beta chain-like [KO:K06752 ]
110199459 HLA class II histocompatibility antigen, DM beta chain isoform X1 [KO:K06752 ]
110199460 HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752 ]
110203128 class I histocompatibility antigen, Gogo-OKO alpha chain-like isoform X1 [KO:K06751 ]
110199325 BOLA class I histocompatibility antigen, alpha chain BL3-7-like [KO:K06751 ]
110199390 DLA class I histocompatibility antigen, A9/A9 alpha chain-like isoform X1 [KO:K06751 ]
110203695 HLA class I histocompatibility antigen, B-8 alpha chain-like [KO:K06751 ]
110223003 HLA class I histocompatibility antigen, B-40 alpha chain-like [KO:K06751 ]
110223021 HLA class I histocompatibility antigen, B-35 alpha chain-like isoform X1 [KO:K06751 ]
110223022 class I histocompatibility antigen, Gogo-OKO alpha chain-like [KO:K06751 ]
110202415 HLA class I histocompatibility antigen, A-69 alpha chain-like isoform X1 [KO:K06751 ]
110202416 class I histocompatibility antigen, Gogo-OKO alpha chain-like isoform X1 [KO:K06751 ]
110218421 class I histocompatibility antigen, F10 alpha chain-like [KO:K06751 ]
110218438 major histocompatibility complex class I-related gene protein-like isoform X1 [KO:K06751 ]
110218444 class I histocompatibility antigen, F10 alpha chain-like [KO:K06751 ]
110199312 H-2 class I histocompatibility antigen, D-D alpha chain-like isoform X1 [KO:K06751 ]
110218465 major histocompatibility complex class I-related gene protein-like isoform X1 [KO:K06751 ]
110199902 HLA class I histocompatibility antigen, A-11 alpha chain-like [KO:K06751 ]
110208066 CD80; T-lymphocyte activation antigen CD80 isoform X1 [KO:K05412 ]
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 pcw04612 Antigen processing and presentation
pcw04660 T cell receptor signaling pathway
KO pathway LinkDB All DBs
