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Combination of RNA interference and virus receptor trap exerts additive antiviral activity in coxsackievirus B3-induced myocarditis in mice

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Combination of RNA interference and virus receptor trap exerts additive antiviral activity in coxsackievirus B3-induced myocarditis in mice. / Stein, Elisabeth A; Pinkert, Sandra; Becher, Peter Moritz; Geisler, Anja; Zeichhardt, Heinz; Klopfleisch, Robert; Poller, Wolfgang; Tschöpe, Carsten; Lassner, Dirk; Fechner, Henry; Kurreck, Jens.

in: J INFECT DIS, Jahrgang 211, Nr. 4, 15.02.2015, S. 613-622.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Stein, EA, Pinkert, S, Becher, PM, Geisler, A, Zeichhardt, H, Klopfleisch, R, Poller, W, Tschöpe, C, Lassner, D, Fechner, H & Kurreck, J 2015, 'Combination of RNA interference and virus receptor trap exerts additive antiviral activity in coxsackievirus B3-induced myocarditis in mice', J INFECT DIS, Jg. 211, Nr. 4, S. 613-622. https://doi.org/10.1093/infdis/jiu504

APA

Stein, E. A., Pinkert, S., Becher, P. M., Geisler, A., Zeichhardt, H., Klopfleisch, R., Poller, W., Tschöpe, C., Lassner, D., Fechner, H., & Kurreck, J. (2015). Combination of RNA interference and virus receptor trap exerts additive antiviral activity in coxsackievirus B3-induced myocarditis in mice. J INFECT DIS, 211(4), 613-622. https://doi.org/10.1093/infdis/jiu504

Vancouver

Stein EA, Pinkert S, Becher PM, Geisler A, Zeichhardt H, Klopfleisch R et al. Combination of RNA interference and virus receptor trap exerts additive antiviral activity in coxsackievirus B3-induced myocarditis in mice. J INFECT DIS. 2015 Feb 15;211(4):613-622. https://doi.org/10.1093/infdis/jiu504

Bibtex

@article{818caf949c9f45e5a5945c417e253d0b,
title = "Combination of RNA interference and virus receptor trap exerts additive antiviral activity in coxsackievirus B3-induced myocarditis in mice",
abstract = "BACKGROUND: Coxsackievirus B3 (CVB3) is a major heart pathogen against which no therapy exists to date. The potential of a combination treatment consisting of a proteinaceous virus receptor trap and an RNA interference-based component to prevent CVB3-induced myocarditis was investigated.METHODS AND RESULTS: A soluble variant of the extracellular domain of the coxsackievirus-adenovirus receptor (sCAR-Fc) was expressed from an adenoviral vector and 2 short hairpin RNAs (shRdRp2.4) directed against CVB3 were delivered by an adeno-associated virus (AAV) vector. Cell culture experiments revealed additive antiviral activity of the combined application. In a CVB3-induced mouse myocarditis model, both components applied individually significantly reduced inflammation and viral load in the heart. The combination exerted an additive antiviral effect and reduced heart pathology. Hemodynamic measurement revealed that infection with CVB3 resulted in impaired heart function, as illustrated by a drastically reduced cardiac output and impaired contractility and relaxation. Treatment with either sCAR-Fc or shRdRp2.4 significantly improved these parameters. Importantly, the combination of both components led to a further significant improvement of heart function.CONCLUSIONS: Combination of sCAR-Fc and shRdRp2.4 exerted additive effects and was significantly more effective than either of the single treatments in inhibiting CVB3-induced myocarditis and preventing cardiac dysfunction.",
keywords = "Animals, Antiviral Agents/metabolism, Coxsackievirus Infections/drug therapy, Disease Models, Animal, Dose-Response Relationship, Drug, Enterovirus B, Human/drug effects, Genetic Therapy/methods, HeLa Cells, Humans, Male, Mice, Mice, Inbred BALB C, Myocarditis/drug therapy, RNA Interference, RNA, Small Interfering/genetics, Receptors, Virus/genetics, Viral Load/drug effects",
author = "Stein, {Elisabeth A} and Sandra Pinkert and Becher, {Peter Moritz} and Anja Geisler and Heinz Zeichhardt and Robert Klopfleisch and Wolfgang Poller and Carsten Tsch{\"o}pe and Dirk Lassner and Henry Fechner and Jens Kurreck",
note = "{\textcopyright} The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.",
year = "2015",
month = feb,
day = "15",
doi = "10.1093/infdis/jiu504",
language = "English",
volume = "211",
pages = "613--622",
journal = "J INFECT DIS",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "4",

}

RIS

TY - JOUR

T1 - Combination of RNA interference and virus receptor trap exerts additive antiviral activity in coxsackievirus B3-induced myocarditis in mice

AU - Stein, Elisabeth A

AU - Pinkert, Sandra

AU - Becher, Peter Moritz

AU - Geisler, Anja

AU - Zeichhardt, Heinz

AU - Klopfleisch, Robert

AU - Poller, Wolfgang

AU - Tschöpe, Carsten

AU - Lassner, Dirk

AU - Fechner, Henry

AU - Kurreck, Jens

N1 - © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

PY - 2015/2/15

Y1 - 2015/2/15

N2 - BACKGROUND: Coxsackievirus B3 (CVB3) is a major heart pathogen against which no therapy exists to date. The potential of a combination treatment consisting of a proteinaceous virus receptor trap and an RNA interference-based component to prevent CVB3-induced myocarditis was investigated.METHODS AND RESULTS: A soluble variant of the extracellular domain of the coxsackievirus-adenovirus receptor (sCAR-Fc) was expressed from an adenoviral vector and 2 short hairpin RNAs (shRdRp2.4) directed against CVB3 were delivered by an adeno-associated virus (AAV) vector. Cell culture experiments revealed additive antiviral activity of the combined application. In a CVB3-induced mouse myocarditis model, both components applied individually significantly reduced inflammation and viral load in the heart. The combination exerted an additive antiviral effect and reduced heart pathology. Hemodynamic measurement revealed that infection with CVB3 resulted in impaired heart function, as illustrated by a drastically reduced cardiac output and impaired contractility and relaxation. Treatment with either sCAR-Fc or shRdRp2.4 significantly improved these parameters. Importantly, the combination of both components led to a further significant improvement of heart function.CONCLUSIONS: Combination of sCAR-Fc and shRdRp2.4 exerted additive effects and was significantly more effective than either of the single treatments in inhibiting CVB3-induced myocarditis and preventing cardiac dysfunction.

AB - BACKGROUND: Coxsackievirus B3 (CVB3) is a major heart pathogen against which no therapy exists to date. The potential of a combination treatment consisting of a proteinaceous virus receptor trap and an RNA interference-based component to prevent CVB3-induced myocarditis was investigated.METHODS AND RESULTS: A soluble variant of the extracellular domain of the coxsackievirus-adenovirus receptor (sCAR-Fc) was expressed from an adenoviral vector and 2 short hairpin RNAs (shRdRp2.4) directed against CVB3 were delivered by an adeno-associated virus (AAV) vector. Cell culture experiments revealed additive antiviral activity of the combined application. In a CVB3-induced mouse myocarditis model, both components applied individually significantly reduced inflammation and viral load in the heart. The combination exerted an additive antiviral effect and reduced heart pathology. Hemodynamic measurement revealed that infection with CVB3 resulted in impaired heart function, as illustrated by a drastically reduced cardiac output and impaired contractility and relaxation. Treatment with either sCAR-Fc or shRdRp2.4 significantly improved these parameters. Importantly, the combination of both components led to a further significant improvement of heart function.CONCLUSIONS: Combination of sCAR-Fc and shRdRp2.4 exerted additive effects and was significantly more effective than either of the single treatments in inhibiting CVB3-induced myocarditis and preventing cardiac dysfunction.

KW - Animals

KW - Antiviral Agents/metabolism

KW - Coxsackievirus Infections/drug therapy

KW - Disease Models, Animal

KW - Dose-Response Relationship, Drug

KW - Enterovirus B, Human/drug effects

KW - Genetic Therapy/methods

KW - HeLa Cells

KW - Humans

KW - Male

KW - Mice

KW - Mice, Inbred BALB C

KW - Myocarditis/drug therapy

KW - RNA Interference

KW - RNA, Small Interfering/genetics

KW - Receptors, Virus/genetics

KW - Viral Load/drug effects

U2 - 10.1093/infdis/jiu504

DO - 10.1093/infdis/jiu504

M3 - SCORING: Journal article

C2 - 25193982

VL - 211

SP - 613

EP - 622

JO - J INFECT DIS

JF - J INFECT DIS

SN - 0022-1899

IS - 4

ER -