{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:53:32Z","timestamp":1791928412734,"version":"4.3.4"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"20","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2019,5,14]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Group B enteroviruses are common causes of acute myocarditis, which can be a precursor of chronic myocarditis and dilated cardiomyopathy, leading causes of heart transplantation. To date, the specific viral functions involved in the development of dilated cardiomyopathy remain unclear.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>Total RNA from cardiac tissue of patients with dilated cardiomyopathy was extracted, and sequences corresponding to the 5\u2019 termini of enterovirus RNAs were identified. After next-generation RNA sequencing, viral cDNA clones mimicking the enterovirus RNA sequences found in patient tissues were generated in vitro, and their replication and impact on host cell functions were assessed on primary human cardiac cells in culture.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>Major enterovirus B populations characterized by 5\u2019 terminal genomic RNA deletions ranging from 17 to 50 nucleotides were identified either alone or associated with low proportions of intact 5\u2019 genomic termini. In situ hybridization and immunohistological assays detected these persistent genomes in clusters of cardiomyocytes. Transfection of viral RNA into primary human cardiomyocytes demonstrated that deleted forms of genomic RNAs displayed early replication activities in the absence of detectable viral plaque formation, whereas mixed deleted and complete forms generated particles capable of inducing cytopathic effects at levels distinct from those observed with full-length forms alone. Moreover, deleted or full-length and mixed forms of viral RNA were capable of directing translation and production of proteolytically active viral proteinase 2A in human cardiomyocytes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>We demonstrate that persistent viral forms are composed of B-type enteroviruses harboring a 5\u2019 terminal deletion in their genomic RNAs and that these viruses alone or associated with full-length populations of helper RNAs could impair cardiomyocyte functions by the proteolytic activity of viral proteinase 2A in cases of unexplained dilated cardiomyopathy. These results provide a better understanding of the molecular mechanisms that underlie the persistence of EV forms in human cardiac tissues and should stimulate the development of new therapeutic strategies based on specific inhibitors of the coxsackievirus B proteinase 2A activity for acute and chronic cardiac infections.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.118.035966","type":"journal-article","created":{"date-parts":[[2019,2,13]],"date-time":"2019-02-13T10:03:41Z","timestamp":1550052221000},"page":"2326-2338","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":76,"title":["Enterovirus Persistence in Cardiac Cells of Patients With Idiopathic Dilated Cardiomyopathy Is Linked to 5\u2019 Terminal Genomic RNA-Deleted Viral Populations With Viral-Encoded Proteinase Activities"],"prefix":"10.1161","volume":"139","author":[{"given":"Alexis","family":"Bouin","sequence":"first","affiliation":[{"name":"EA-4684 Cardiovir, Faculty of Medicine, University of Reims Champagne-Ardenne, Reims, France (A.B., P.-A.G., M.W., F.R., Y.N., A.R., P.F., L.A.)."},{"name":"Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine (A.B., M.N.V., B.L.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul-Antoine","family":"Gretteau","sequence":"additional","affiliation":[{"name":"EA-4684 Cardiovir, Faculty of Medicine, University of Reims Champagne-Ardenne, Reims, France (A.B., P.-A.G., M.W., F.R., Y.N., A.R., P.F., L.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Wehbe","sequence":"additional","affiliation":[{"name":"EA-4684 Cardiovir, Faculty of Medicine, University of Reims Champagne-Ardenne, Reims, France (A.B., P.-A.G., M.W., F.R., Y.N., A.R., P.F., L.A.)."},{"name":"Centre AZM pour la recherche en biotechnologie et ses applications, Universit\u00e9 Libanaise, Tripoli, Lebanon (M.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanny","family":"Renois","sequence":"additional","affiliation":[{"name":"EA-4684 Cardiovir, Faculty of Medicine, University of Reims Champagne-Ardenne, Reims, France (A.B., P.-A.G., M.W., F.R., Y.N., A.R., P.F., L.A.)."},{"name":"LUNAM University, Oniris, LABERCA, UMR INRA 1329, Nantes, France (F.R.)."},{"name":"CHU Robert Debr\u00e9, Laboratoire de Virologie M\u00e9dicale et Mol\u00e9culaire, Reims, France (F.R., Y.N., N.L., P.F., L.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohan","family":"N\u2019Guyen","sequence":"additional","affiliation":[{"name":"EA-4684 Cardiovir, Faculty of Medicine, University of Reims Champagne-Ardenne, Reims, France (A.B., P.-A.G., M.W., F.R., Y.N., A.R., P.F., L.A.)."},{"name":"CHU Robert Debr\u00e9, Laboratoire de Virologie M\u00e9dicale et Mol\u00e9culaire, Reims, France (F.R., Y.N., N.L., P.F., L.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"L\u00e9v\u00eaque","sequence":"additional","affiliation":[{"name":"CHU Robert Debr\u00e9, Laboratoire de Virologie M\u00e9dicale et Mol\u00e9culaire, Reims, France (F.R., Y.N., N.L., P.F., L.A.)."},{"name":"EA-4331 LITEC, Faculty of Medicine and Pharmacy, University Hospital of Poitiers, France (N.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle N.","family":"Vu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine (A.B., M.N.V., B.L.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Tracy","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha (S.T., N.M.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora M.","family":"Chapman","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha (S.T., N.M.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Bruneval","sequence":"additional","affiliation":[{"name":"Service d\u2019Anatomie Pathologique, H\u00f4pital Europ\u00e9en Georges Pompidou, Paris, France (P.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Fornes","sequence":"additional","affiliation":[{"name":"EA-4684 Cardiovir, Faculty of Medicine, University of Reims Champagne-Ardenne, Reims, France (A.B., P.-A.G., M.W., F.R., Y.N., A.R., P.F., L.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bert L.","family":"Semler","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine (A.B., M.N.V., 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