Download A Geographical Mystery: Do Cardiotropic Viruses Respect National

Journal of the American College of Cardiology
© 2008 by the American College of Cardiology Foundation
Published by Elsevier Inc.
Vol. 52, No. 1, 2008
ISSN 0735-1097/08/$34.00
CORRESPONDENCE
Letters to the Editor
A Geographical Mystery:
Do Cardiotropic Viruses
Respect National Borders?
(polymerase chain reaction primers?) in identifying small amounts
of viral genome. Whatever the reason for this discrepancy, it is
important to verify the findings of Andréoletti et al. (1) in other
labs with experience in identifying very small amounts of viral
genomes in human myocardium.
We read the interesting article of Andréoletti et al. (1) showing
active coxsackieviral B (CV-B) infection in post-mortem endomyocardial tissue of patients who died suddenly due to acute
myocardial infarction. The demonstration of sarcolemmal dystrophin disruption in the same tissue areas that were infected by
CV-B is of potential groundbreaking value for the understanding
of viral pathogen-induced myocardial damage in humans. Both
CV-B genomes and CV-B capsid proteins were detected in the
heart tissues of patients with myocardial infarction by reverse
transcriptase-polymerase chain reaction and immunohistochemistry, thereby suggesting active virus replication.
However, it is interesting to find that about one-half of the
myocytes (exemplary pictured in Fig. 1 of this article [1]) reveal
virus replication in patients with coronary artery disease as demonstrated by the presence of the enteroviral VP1 capsid protein (1).
Previous extensive investigations regarding immunohistochemical
stainings for the detection of enteroviral proteins in cardiac tissue
by applying the antibody from clone 5-D8/1 (Dako, Glostrup,
Denmark), which was also applied in this study, revealed a
considerable unspecific cross-reaction with uninfected necrotic or
apoptotic human cardiomyocytes (2). In fact, using this antibody,
we found that false positive staining of cardiomyocytes can be
detected in all kinds of cardiac diseases where affected cardiomyocytes are present including patients with myocardial infarction and
coronary artery disease. Therefore, the suitability of this antibody
for the visualization of CV-B capsid proteins is questionable at
least in diseased hearts.
In addition, it is surprising that Andréoletti et al. (1) found
enteroviruses to be the only cardiotropic viral agents active in
France. In contrast, endomyocardial biopsies in Germany consistently and almost exclusively contain parvovirus B19 (PVB19) and
human herpes virus type 6 whereas CV-B is a rare finding (3–7).
As PVB19 may lead to endothelial dysfunction (8,9) and is found
in the majority of patients with a clinical picture of acute
myocardial infarction despite a normal coronary anatomy (10), one
might expect to find also PVB19 genomes in French patients dying
of acute myocardial infarction. Of course, there are very little data
on endomyocardial biopsy findings in German patients with acute
myocardial infarction, and it cannot be excluded that one would
find CV-B in such a cohort.
How can this astonishing difference between endomyocardial
biopsy findings in French and German people be explained? Is
viral disease of the heart a locally restricted phenomenon? Does
CV-B show a tropism for wine-drinking humans while PVB19 is
mainly attracted to beer drinkers? Is there a mechanism preventing
viruses from crossing the French-German border? Or is the
difference not a real one, but is due to methodological differences
Ali Yilmaz, MD
Karin Klingel, MD
Reinhard Kandolf, MD
*Udo Sechtem, MD
*Robert-Bosch-Krankenhaus
Auerbachstrasse 110
70376 Stuttgart
Germany
E-mail: [email protected]
doi:10.1016/j.jacc.2008.01.072
REFERENCES
1. Andréoletti L, Venteo L, Douche-Aourik F, et al. Active coxsackieviral B infection is associated with disruption of dystrophin in endomyocardial tissue of patients who died suddenly of acute myocardial
infarction. J Am Coll Cardiol 2007;50:2207–14.
2. Klingel K, Sauter M, Bock CT, Szalay G, Schnorr JJ, Kandolf R.
Molecular pathology of inflammatory cardiomyopathy. Med Microbiol
Immunol 2004;193:101–7.
3. Kuhl U, Pauschinger M, Noutsias M, et al. High prevalence of viral
genomes and multiple viral infections in the myocardium of adults
with “idiopathic” left ventricular dysfunction. Circulation 2005;111:
887–93.
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8. Vallbracht KB, Schwimmbeck PL, Kuhl U, Seeberg B, Schultheiss
HP. Endothelium-dependent flow-mediated vasodilation of systemic
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Circulation 2004;110:2938 – 45.
9. Vallbracht KB, Schwimmbeck PL, Kuhl U, Rauch U, Seeberg B,
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mimicking acute myocardial infarction. Circulation 2003;108:945–50.
Reply
Our multicentric French case-control study demonstrates for the
first time that enteroviruses (EVs) may significantly contribute to
the pathogenesis of acute myocardial infarction (MI) (1). These