| Entry |
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| Name |
Viral myocarditis
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| 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.
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| Class |
Human Diseases; Cardiovascular diseases
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| Pathway map |
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| Disease |
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| Orthology |
| coxsackievirus and adenovirus receptor | | decay accelerating factor | | tyrosine-protein kinase Fyn [EC: 2.7.10.2] | | caveolin 1 | | abelson tyrosine-protein kinase 1 [EC: 2.7.10.2] | | abelson tyrosine-protein kinase 2 [EC: 2.7.10.2] | | Ras-related C3 botulinum toxin substrate 1 | | Ras-related C3 botulinum toxin substrate 2 | | Ras-related C3 botulinum toxin substrate 3 | | delta-sarcoglycan | | gamma-sarcoglycan | | alpha-sarcoglycan | | beta-sarcoglycan | | dystroglycan 1 | | dystrophin | | actin beta/gamma 1 | | translation initiation factor 4G | | cyclin D1 | | | | BH3 interacting domain death agonist | | cytochrome c | | | | | | myosin heavy chain | | tumor necrosis factor ligand superfamily member 5 | | tumor necrosis factor receptor superfamily member 5 | | major histocompatibility complex, class II | | T cell receptor alpha chain V region | | T-cell receptor beta chain V region | | major histocompatibility complex, class I | | CD80 antigen | | CD86 antigen | | CD28 antigen | | perforin 1 | | integrin alpha L | | integrin beta 2 | | intercellular adhesion molecule 1 | | immunoglobulin heavy chain |
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| Reference |
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| Authors |
Esfandiarei M, McManus BM |
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| Title |
Molecular biology and pathogenesis of viral myocarditis. |
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| Journal |
Annu Rev Pathol 3:127-55 (2008) |
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| Reference |
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| Authors |
Badorff C, Knowlton KU |
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| Title |
Dystrophin disruption in enterovirus-induced myocarditis and dilated cardiomyopathy: from bench to bedside. |
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| Journal |
Med Microbiol Immunol 193:121-6 (2004) |
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| Reference |
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| Authors |
Maekawa Y, Ouzounian M, Opavsky MA, Liu PP |
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| Title |
Connecting the missing link between dilated cardiomyopathy and viral myocarditis: virus, cytoskeleton, and innate immunity. |
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| Journal |
Circulation 115:5-8 (2007) |
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| Reference |
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| Authors |
Pankuweit S, Portig I, Maisch B |
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| Title |
Pathophysiology of cardiac inflammation: molecular mechanisms. |
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| Journal |
Herz 27:669-76 (2002) |
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| Reference |
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| Authors |
Gao G, Luo H |
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| Title |
The ubiquitin-proteasome pathway in viral infections. |
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| Journal |
Can J Physiol Pharmacol 84:5-14 (2006) |
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| Reference |
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| Authors |
Coyne CB, Bergelson JM |
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| Title |
Virus-induced Abl and Fyn kinase signals permit coxsackievirus entry through epithelial tight junctions. |
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| Journal |
Cell 124:119-31 (2006) |
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| Reference |
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| Authors |
Badorff C, Lee GH, Knowlton KU |
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| Title |
Enteroviral cardiomyopathy: bad news for the dystrophin-glycoprotein complex. |
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| Journal |
Herz 25:227-32 (2000) |
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| Reference |
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| Authors |
Knowlton KU |
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| Title |
CVB infection and mechanisms of viral cardiomyopathy. |
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| Journal |
Curr Top Microbiol Immunol 323:315-35 (2008) |
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| Reference |
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| Authors |
Castellano G, Affuso F, Di Conza P, Fazio S |
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| Title |
Myocarditis and dilated cardiomyopathy: possible connections and treatments. |
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| Journal |
J Cardiovasc Med (Hagerstown) 9:666-71 (2008) |
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| Reference |
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| Authors |
Cooper LT Jr |
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| Title |
Myocarditis. |
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| Journal |
N Engl J Med 360:1526-38 (2009) |
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| Reference |
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| Authors |
Kawai C |
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| Title |
From myocarditis to cardiomyopathy: mechanisms of inflammation and cell death: learning from the past for the future. |
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| Journal |
Circulation 99:1091-100 (1999) |
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| Reference |
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| Authors |
Liu PP, Mason JW |
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| Title |
Advances in the understanding of myocarditis. |
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| Journal |
Circulation 104:1076-82 (2001) |
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| Reference |
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| Authors |
Mason JW |
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| Title |
Myocarditis and dilated cardiomyopathy: an inflammatory link. |
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| Journal |
Cardiovasc Res 60:5-10 (2003) |
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| Reference |
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| Authors |
Tam PE |
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| Title |
Coxsackievirus myocarditis: interplay between virus and host in the pathogenesis of heart disease. |
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| Journal |
Viral Immunol 19:133-46 (2006) |
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