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Molecular mechanisms and cellular consequences of enterovirus persistence in cardiomyocytes

Objective

Enteroviruses (EV) are small naked single-stranded positive RNA viruses of approximately 7,400 nucleotides. Their genome is flanked on the 5' end by a non-coding region (NCR), which is crucial for the initiation of the replication and translation of the viral genome. Enteroviruses are common human pathogens, transmitted through fecal-oral and respiratory routes. Although the majority of EV infections remain asymptomatic, these viruses, especially group B coxsackieviruses (CVB), are considered to be a common cause of acute myocarditis in children and young adults, a disease which is a precursor to 10-20% of chronic myocarditis cases as well as dilated cardiomyopathy (DCM, prevalence = 7 cases / 100,000, second leading cause of heart transplantation worldwide after ischemic heart disease). However, the viral molecular mechanisms involved in the progression of acute myocarditis to chronic myocarditis and subsequently to DCM are currently poorly understood, thereby limiting the development of new specific therapeutic strategies. In 2011, our research team (EA-4684 CardioVir/FRS CAP-santé, University of Reims Champagne-Ardenne) reported CVB strains presenting with genomic 5’ terminal deletions ranging in size from 15 to 35 nucleotides in explanted heart tissue collected from patients suffering from idiopathic DCM. These deletions could explain how the virus can persist in the heart long after the acute infection leading to the development of chronic cardiomyopathies. The objectives of this proposal are to determine the mechanisms by which deleted EV ensure the translation and replication of their genomes and to assess the effects of persistent infection on the structures and functions of infected cardiac myocytes. A better understanding of the molecular mechanisms implicated in viral persistence will stimulate the research into new therapeutic strategies to prevent and treat chronic infections caused by EV.

Call for proposal

FP7-PEOPLE-2013-IOF
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Funding Scheme

MC-IOF - International Outgoing Fellowships (IOF)

Coordinator

UNIVERSITE DE POITIERS
Address
Rue De L Hotel Dieu 15 Hotel Pinet
86034 Poitiers Cedex
France
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 156 863,40
Administrative Contact
Jean-Marie Pincemin (Mr.)

Participants (1)

UNIVERSITE DE REIMS CHAMPAGNE-ARDENNE

Participation ended

France
Address
Boulevard De La Paix 9 Villa Douce
51100 Reims
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Nathalie Rau (Ms)