Fachbereich Veterinärmedizin



    Combination of RNA Interference and Virus Receptor Trap Exerts Additive Antiviral Activity in Coxsackievirus B3-induced Myocarditis in Mice (2015)

    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Stein, Elisabeth A
    Pinkert, Sandra
    Becher, Peter Moritz
    Geisler, Anja
    Zeichhardt, Heinz
    Klopfleisch, Robert (WE 12)
    Poller, Wolfgang
    Tschöpe, Carsten
    Lassner, Dirk
    Fechner, Henry
    Kurreck, Jens
    The Journal of infectious diseases; 211(4) — S. 613–622
    ISSN: 0022-1899
    DOI: 10.1093/infdis/jiu504
    Pubmed: 25193982
    Institut für Tierpathologie

    Robert-von-Ostertag-Str. 15
    Gebäude 12
    14163 Berlin
    +49 30 838 62450

    Abstract / Zusammenfassung

    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.

    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.

    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.