Entry
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
BRITE hierarchy
Pathway map
Ortholog table
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 ]
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 ]
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 ]
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 ]
105298423 CD28; T-cell-specific surface glycoprotein CD28 isoform X1 [KO:K06470 ]
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 pathway
pvp04612 Antigen processing and presentation
pvp04660 T cell receptor signaling pathway
KO pathway
LinkDB
All DBs