Prevention of cardiac dysfunction in acute coxsackievirus B3 cardiomyopathy by inducible expression of a soluble coxsackievirus-adenovirus receptor

Circulation
Sandra PinkertHenry Fechner

Abstract

Group B coxsackieviruses (CVBs) are the prototypical agents of acute myocarditis and chronic dilated cardiomyopathy, but an effective targeted therapy is still not available. Here, we analyze the therapeutic potential of a soluble (s) virus receptor molecule against CVB3 myocarditis using a gene therapy approach. We generated an inducible adenoviral vector (AdG12) for strict drug-dependent delivery of sCAR-Fc, a fusion protein composed of the coxsackievirus-adenovirus receptor (CAR) extracellular domains and the carboxyl terminus of human IgG1-Fc. Decoy receptor expression was strictly doxycycline dependent, with no expression in the absence of an inducer. CVB3 infection of HeLa cells was efficiently blocked by supernatant from AdG12-transduced cells, but only in the presence of doxycycline. After liver-specific transfer, AdG12 (plus doxycycline) significantly improved cardiac contractility and diastolic relaxation compared with a control vector in CVB3-infected mice if sCAR-Fc was induced before infection (left ventricular pressure 59+/-3.8 versus 45.4+/-2.7 mm Hg, median 59 versus 45.8 mm Hg, P<0.01; dP/dt(max) 3645.1+/-443.6 versus 2057.9+/-490.2 mm Hg/s, median 3526.6 versus 2072 mm Hg/s, P<0.01; and dP/dt(min) -2125.5+/-33...Continue Reading

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Citations

Feb 27, 2013·Molecular Therapy : the Journal of the American Society of Gene Therapy·Anja GeislerHenry Fechner
Dec 25, 2010·European Heart Journal·S Van LinthoutC Tschöpe
Jun 28, 2011·European Heart Journal·Heinz-Peter SchultheissLeslie T Cooper
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Jun 29, 2018·Journal of Clinical and Translational Hepatology·Wolfgang PollerUlf Landmesser
Apr 30, 2020·International Journal of Molecular Sciences·Soo-Hyeon YunEun-Seok Jeon
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May 1, 2021·Viruses·Anja GeislerHenry Fechner
Oct 6, 2021·Cardiovascular Research·Heinz-Peter SchultheissFelicitas Escher

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