Cardiovascular Research Advance Access [Accepted Manuscript] published online on October 11, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn276
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The proapoptotic protein Siva binds to the muscle protein Telethonin in cardiomyocytes during coxsackieviral infection
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1 Leibniz Institute for Natural Product Research and Infection Biology e. V. – Hans-Knöll-Institute, Department of Cell and Molecular Biology, Beutenbergstr. 11a, D-07745 Jena, Germany
2 Leibniz Institute for Age Research e. V. – Fritz-Lipmann-Institute, Department of Biomolecular NMR spectroscopy, Beutenbergstr. 11a, D-07745 Jena, Germany
3 Institute of Virology and Antiviral Therapy, Medical Center, Friedrich Schiller University Jena, Hans-Knöll-Str. 2, D-07745 Jena, Germany
* Corresponding author: Thomas Munder, University of Applied Sciences Jena, Department of Medical Engineering and Biotechnology, Carl-Zeiss-Promenade 2, D-07745 Jena, Germany, Tel: +49 36 41 205 660. Fax: +49 36 41 205 601. Electronic mail address: Thomas.Munder{at}fh-jena.de
Aims.: Coxsackievirus B3 (CVB3) is known to cause a variety of human diseases including acute and chronic myocarditis as well as dilated cardiomyopathy. However, the mechanisms by which CVB3 causes diseases are not well understood.
Methods and results.: Studies identifying protein-protein interactions during CVB3-infection are useful in delineating the pathogenesis of acute or chronic myocarditis. Screening a human heart cDNA library revealed a yet unknown interaction partner of the proapoptotic protein Siva. We demonstrate that Siva specifically interacts with the heart and skeletal muscle protein Telethonin. The expression of Siva is increased in heart tissue of CVB3-infected mice and both proteins colocalize in cardiomyocytes.
Conclusion.: Telethonin might be involved in CVB3-mediated formation of cell damages and in the resulting heart function failures due to the interaction with Siva. We suggest a molecular mechanism through which coxsackieviral infection contributes to the pathogenesis of chronic myocarditis and in particular of acquired forms of dilated cardiomyopathy.
KEYWORDS Cardiomyocytes; Colocalization; Coxsackievirus B3; Siva; Telethonin
Time for primary review: 41 days
Present address: University of Applied Sciences Jena, Department of Medical Engineering and Biotechnology, Carl-Zeiss-Promenade 2, D-07745 Jena, Germany