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CLINICAL RESEARCH

Active Coxsackieviral B Infection Is Associated With Disruption of Dystrophin in Endomyocardial Tissue of Patients Who Died Suddenly of Acute Myocardial Infarction

Laurent Andréoletti, MD, PhD^_*,_*, Lydie Ventéo, MSci, Fatima Douche-Aourik, PhD, Frédéric Canas, MD, Geoffroy Lorin de la Grandmaison, MD, PhD, Jérôme Jacques, MSci^_*, Hélène Moret, PhD^_*, Nicolas Jovenin, MD^||, Jean-François Mosnier, MD, PhD^¶, Mathieu Matta, MSci^_*, Sébastien Duband, MD^#, Michel Pluot, MD, Bruno Pozzetto, MD, PhD and Thomas Bourlet, MD, PhD

^_* Laboratoire de Virologie Médicale et Moléculaire et Faculté de Médecine (EA-3798), Reims, France
Service d'Anatomie Pathologique, Centre Hospitalier Universitaire, Reims, France
Laboratoire de Bactériologie-Virologie, Centre Hospitalier Universitaire, Saint-Etienne, France
Service d'Anatomie Pathologique et de Médecine Légale, Hôpital Raymond Poincaré, Garches, France
^|| Département d'Information Médicale, Centre Hospitalier Universitaire et Faculté de Médecine de Reims, Reims, France
^¶ Service d'Anatomie Pathologique, Centre Hospitalier Universitaire, Nantes, France
^# Service d'Anatomie Pathologique, Centre Hospitalier Universitaire, Saint-Etienne, France

Manuscript received May 3, 2007; revised manuscript received July 9, 2007, accepted July 30, 2007.

^_* Reprint requests and correspondence: Prof. Laurent Andréoletti, Laboratoire de Virologie Médicale et Moléculaire et Faculté de Médecine (EA-3798), Hôpital Robert Debré, Avenue du Général Koenig, 51092 Reims Cedex, France. (Email: landreoletti{at}chu-reims.fr).

Objectives: In this study, we evaluated the potential direct role of enterovirus (EV) cardiac infections in the pathogenesis of myocardial infarction (MI).

Background: Enteroviruses (Picornaviridae) have been suspected to play a role in the development of acute MI.

Methods: The presence of EV ribonucleic acid (RNA) sequences and capsid viral protein 1 (VP1) and the virus-mediated focal disruption of dystrophin were retrospectively investigated by reverse transcriptase-polymerase chain reaction and immunohistochemistry assays in endomyocardial tissues of patients who died suddenly of acute MI by comparison with similar samples of control patients matched for gender, residence area, and year of death.

Results: Enterovirus infection markers were detected in 20 (40%) of 50 patients who died suddenly of MI, 2 (4%) of 50 matched subjects without cardiac disease (p < 0.001), and 4 (8%) of 50 matched patients exhibiting a noncoronary chronic cardiopathy (p < 0.001). All of the EV RNA-positive patients exhibited VP1, which provided evidence of viral protein synthesis activity. The VP1 gene sequences amplified after cloning from myocardial or coronary samples of 8 of the MI patients and showed a strong homology with sequences of coxsackievirus B2 and B3 serotypes. Moreover, in the endomyocardial tissue of these 8 patients, immunohistochemical analyses demonstrated that there was disruption of the sarcolemmal localization of dystrophin in the same tissue areas that were infected by coxsackieviruses.

Conclusions: Our findings demonstrate a significantly higher proportion of active coxsackievirus B cardiovascular infections in patients who suddenly died of MI compared with matched control subjects, suggesting that these EVs may significantly contribute to the pathogenesis of acute MI by a focal disruption of the dystrophin-glycoprotein complex.

Abbreviations and Acronyms   CV-B = coxsackievirus B   EV = enterovirus   MI = myocardial infarction   VP1 = capsid viral protein 1

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