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The molecular basis of cardiotropic viral infections

W. Poller*, H. Fechner, M. Noutsias, C. Tschoepe, M. Pauschinger and H.-P. Schultheiss

Department of Cardiology and Pneumology, University Hospital Benjamin Franklin, Freie Universität Berlin, Berlin, Germany

* Correspondence: Prof. Dr med. Wolfgang Poller, Department of Cardiology and Pneumology, University Hospital Benjamin Franklin, Freie Universität Berlin, Hindenburgdamm 30, D-12200 Berlin, Germany.

Abstract

The molecular determinants of cardiac viral infections are currently under intense investigation because an understanding of these determinants may lead to an explanation for the highly variable clinical courses of viral heart diseases. Several articles in this volume deal with basic structures that are involved in virus entry and migration, switching between viral persistence and replication, and intracellular signals and immune reactions triggered by viruses. We focus upon the first area, in which recent studies have provided new insights of possible clinical and therapeutic relevance. Coxsackieviruses and adenoviruses are common agents in viral heart disease. In the majority of exposed individuals they do not cause myocardial disease, however. In 1997 a common receptor for the two viruses — the coxsackievirus-adenovirus-receptor (CAR) — was cloned which is a key determinant of cellular uptake of both viruses. We observed highly variable expression patterns for CAR in humans. Healthy donor hearts had low levels of CAR, whereas explanted hearts of patients with dilated cardiomyopathy (DCM) exhibited high CAR expression in their myocardium. Heart failure per se was not associated with CAR induction. Recombinant overexpression of human CAR in cardiomyocytes strongly increased their virus uptake rate, suggesting that CAR induction enhances cardiac vulnerability to viral heart diseases. Receptor induction may aggravate the clinical disease course, and therefore blockade of receptor expression or receptor-virus interactions offers new therapeutic perspectives. A broader analysis of the cardiovascular expression patterns of receptors for other viruses and virus-derived gene therapy vectors should lead to a better understanding of individual risk factors for viral heart diseases and their highly variable clinical courses, and lead to new therapeutic options, including advanced gene therapeutic strategies.

Key Words: Coxsackievirus adenovirus receptor • dilated cardiomyopathy • disease predispositions • viral heart disease • virus receptors

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