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Treatment of coxsackievirus-B3-infected BALB/c mice with the soluble coxsackie adenovirus receptor CAR4/7 aggravates cardiac injury

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Abstract

Coxsackie adenovirus receptor (CAR) is involved in immunological processes, and its soluble isoforms have antiviral effects on coxsackievirus B3 (CVB3) infection in vitro. We explored in this study the impact of CAR4/7, a soluble CAR isoform, on CVB3-induced myocarditis in BALB/c mice. BALB/c mice were treated daily with recombinant CAR4/7, β-galactosidase (β-Gal; as control protein) or buffer for 9 days. Half of each group was infected with CVB3 on day 3, and all mice were killed on day 9. Myocardial CVB3 titer, histology, and serology were analyzed. Treatment with CAR4/7 led to a significant reduction of myocardial CVB3 titer, whereas the application of β-Gal had no detectable effect on the myocardial virus load. CAR4/7 application, however, resulted in increased myocardial inflammation and tissue damage in CVB3-infected hearts, whereas β-Gal caused a degree of cardiac inflammation and injury similar to that in buffer-treated CVB3-infected control animals. CAR4/7 and β-Gal treatment induced the production of antibodies against the respective antigens. CAR4/7-, but not β-Gal-specific, virus-negative sera reacted against myocardial tissue and cellular membranous CAR, and significantly inhibited CVB3 infection in vitro. Thus, CAR4/7 suppressed CVB3 infection in vivo, supporting the concept of receptor analog in antiviral therapy. However, CAR4/7 treatment also leads to an aggravation of myocardial inflammation and injury most likely secondary to an autoimmune process.

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Acknowledgement

Financial support of “Otto-Kuhn-Stiftung im Stifterverband für die Deutsche Wissenschaft” is gratefully acknowledged.

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Authors and Affiliations

  1. Department of Cardiology and Pneumonology, Charité University of Medicine, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany

    A. Dörner, K. Chandrasekharan, H. Fechner, A. Isik, M. Pauschinger & H.-P. Schultheiss

  2. Department of Virology, Charité University of Medicine, Campus Benjamin Franklin, Berlin, Germany

    H.-P. Grunert, V. Lindig & H. Zeichhardt

  3. Division of Cardiology, University of California Medical Center, San Diego, CA, USA

    K. U. Knowlton

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  1. A. Dörner
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  2. H.-P. Grunert
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Correspondence to A. Dörner.

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Dörner, A., Grunert, HP., Lindig, V. et al. Treatment of coxsackievirus-B3-infected BALB/c mice with the soluble coxsackie adenovirus receptor CAR4/7 aggravates cardiac injury. J Mol Med 84, 842–851 (2006). https://doi.org/10.1007/s00109-006-0076-y

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  • DOI: https://doi.org/10.1007/s00109-006-0076-y

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