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is an inflammation of the heart, most commonly cause by viral infections. Amongst the viruses capable of causing myocarditis, CVB3 is a common agent identified in inducing cardiac damage. Internalization of the virus into myocytes occurs by binding to coxsackievirus-adenovirus receptors (CAR) located
146:
and other phagocytic immune cells with Fc receptor recognition bind to the sCAR-Fc-viral complex to eliminate the virus. Essentially, sCAR-Fc mimics CAR receptors on cardiac cells, competitively inhibiting viral attachment and entry into myocytes. Decreased lesions in cardiac tissues, reduced cell
98:
can occur by day three after infection as incubated viruses lyse myocytes, resulting in severe and rapid cardiac decompensation. With loss of cardiac cells increasing progressively, infected individual will experience abnormalities in left ventricular systolic and diastolic function, as well as
122:
in the myocardium during days 7-14 play important roles in both viral clearance and immune mediated cardiac damage. T-cells not only lyse and destroy infected myocytes, but due to molecular mimicry, they also destroy normal, healthy cardiac cells, further driving the heart towards dilated
162:
Administration of sCAR-Fc beyond three days after initial exposure to the virus does not have any beneficial effects as cardiac damage is too severe. As such, the use of sCAR-Fc is currently limited to prophylactic treatments.
188:
Werk D, Pinkert S, Heim A, et al. (September 2009). "Combination of soluble coxsackievirus-adenovirus receptor and anti-coxsackievirus siRNAs exerts synergistic antiviral activity against coxsackievirus B3".
114:(NK cells) at the site of infection limits viral proliferation in myocytes. Conversely, while certain cytokines released from immune cells have protective effects, others such as
502:"Interaction with coxsackievirus and adenovirus receptor, but not with decay-accelerating factor (DAF), induces A-particle formation in a DAF-binding coxsackievirus B3 isolate"
94:
on cell membranes. Once inside the cytoplasm, the virus can use the host's ribosomal machinery to proliferate and replicate progenies for further infection. Extensive cardiac
231:"Inhibition of coxsackie B virus infection by soluble forms of its receptors: binding affinities, altered particle formation, and competition with cellular receptors"
147:
necrosis, and diminished inflammatory responses are observed in sCAR-Fc treated cells (CITE). This suggests protective effects against myocardial damage by CVB3.
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protein, VP4. This irreversible reaction prevents the virus from interacting with cellular receptors (CAR) on cardiac cells, decreasing infectivity of CVB3.
85:
family. Once the virus penetrates the host's systemic circulation via contaminated water or food, it can travel and infect the heart and cause myocarditis.
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The role of the immune system in response to the presence of a virus has both beneficial and detrimental effects on the cardiac system. The arrival of
64:
414:
Herzum M, Ruppert V, Küytz B, Jomaa H, Nakamura I, Maisch B (July 1994). "Coxsackievirus B3 infection leads to cell death of cardiac myocytes".
280:"Soluble recombinant coxsackievirus and adenovirus receptor abrogates coxsackievirus b3-mediated pancreatitis and myocarditis in mice"
55:
B3 (CVB) infections. Coxsackievirus B3 can cause cardiac damage, eventually resulting in a weakened and enlarged heart that is termed
107:
decreases substantially. The cytolytic destruction of heart cells can lead to dilated cardiomyopathy if not treated appropriately.
365:"The innate immune response to coxsackievirus B3 predicts progression to cardiovascular disease and heart failure in male mice"
150:
Conformational changes in a viral particle (A-particle) with sCAR-Fc-virus binding causing the loss of the virus’ internal
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A synthetic and soluble form of CAR (sCAR) has been created to prevent viral infection with CVB3. Attaching Fc domain of
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451:"Pharmacological and biological antiviral therapeutics for cardiac coxsackievirus infections"
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Milstone AM, Petrella J, Sanchez MD, Mahmud M, Whitbeck JC, Bergelson JM (January 2005).
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118:(TNFα) have deleterious effects on heart cells. Moreover, peak concentrations of
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63:, sCAR-Fc prevents the virus entering the cell by competitively binding to
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Goodfellow IG, Evans DJ, Blom AM, et al. (September 2005).
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Yanagawa B, Spiller OB, Proctor DG, et al. (April 2004).
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Fechner H, Pinkert S, Geisler A, Poller W, Kurreck J (2011).
59:. While many other treatments inhibit viral proliferation in
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Onyimba JA, Coronado MJ, Garton AE, et al. (2011).
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to sCAR (sCAR-Fc) enhances solubility and extends its
51:) is an experimental prophylactic treatment against
23:
18:
142:. Furthermore, once sCAR-Fc binds the virus,
99:electrical conduction defects manifesting as
8:
75:Coxsackievirus B3 is a single-stranded RNA
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65:coxsackie virus and adenovirus receptors
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7:
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67:(CAR) on the membrane of myocytes.
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247:10.1128/JVI.79.18.12016-12024.2005
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203:10.1016/j.antiviral.2009.07.002
1:
518:10.1128/JVI.79.1.655-660.2005
321:"Viral myocarditis. A review"
319:Woodruff JF (November 1980).
116:tumor necrosis factor-alpha
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468:10.3390/molecules16108475
49:Soluble Receptor Analogue
31:
27:Soluble receptor analogue
428:10.1006/jmcc.1994.1108
57:dilated cardiomyopathy
416:J. Mol. Cell. Cardiol
382:10.1186/2042-6410-2-2
112:natural killer cells
101:cardiac dysrhythmias
79:and a member of the
565:Medical treatments
105:ejection fraction
42:
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461:(10): 8475–503.
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241:(18): 12016–24.
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123:cardiomyopathy.
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103:. As a result,
92:tight junctions
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560:Heart diseases
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297:10.1086/382598
284:J. Infect. Dis
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197:(3): 298–306.
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158:Administration
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133:immunoglobulin
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53:coxsackievirus
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512:(1): 655–60.
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422:(7): 907–13.
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331:(2): 425–84.
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290:(8): 1431–9.
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144:macrophages
87:Myocarditis
77:enterovirus
71:Myocarditis
24:Other names
549:Categories
167:References
455:Molecules
140:half-life
127:Mechanism
536:15596863
506:J. Virol
487:21989310
401:21338512
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235:J. Virol
211:19591879
96:necrosis
61:myocytes
555:Therapy
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120:T cells
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302:PMID
261:PMID
207:PMID
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522:PMC
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