{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:59:33Z","timestamp":1790517573293,"version":"4.1.0"},"reference-count":80,"publisher":"American Society for Microbiology","issue":"16","license":[{"start":{"date-parts":[[2017,8,15]],"date-time":"2017-08-15T00:00:00Z","timestamp":1502755200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"George Hewitt Foundation for Medical Research"},{"DOI":"10.13039\/100014269","name":"Philippe Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100014269","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Marie Curie International Outgoing Fellowship","award":["622308"],"award-info":[{"award-number":["622308"]}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI022693"],"award-info":[{"award-number":["AI022693"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI026765"],"award-info":[{"award-number":["AI026765"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2017,8,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Group B coxsackieviruses are responsible for chronic cardiac infections. However, the molecular mechanisms by which the virus can persist in the human heart long after the signs of acute myocarditis have abated are still not completely understood. Recently, coxsackievirus B3 strains with 5\u2032-terminal deletions in genomic RNAs were isolated from a patient suffering from idiopathic dilated cardiomyopathy, suggesting that such mutant viruses may be the forms responsible for persistent infection. These deletions lacked portions of 5\u2032 stem-loop I, which is an RNA secondary structure required for viral RNA replication. In this study, we assessed the consequences of the genomic deletions observed\n            <jats:italic>in vivo<\/jats:italic>\n            for coxsackievirus B3 biology. Using cell extracts from HeLa cells, as well as transfection of luciferase replicons in two types of cardiomyocytes, we demonstrated that coxsackievirus RNAs harboring 5\u2032 deletions ranging from 7 to 49 nucleotides in length can be translated nearly as efficiently as those of wild-type virus. However, these 5\u2032 deletions greatly reduced the synthesis of viral RNA\n            <jats:italic>in vitro<\/jats:italic>\n            , which was detected only for the 7- and 21-nucleotide deletions. Since 5\u2032 stem-loop I RNA forms a ribonucleoprotein complex with cellular and viral proteins involved in viral RNA replication, we investigated the binding of the host cell protein PCBP2, as well as viral protein 3CD\n            <jats:sup>pro<\/jats:sup>\n            , to deleted positive-strand RNAs corresponding to the 5\u2032 end. We found that binding of these proteins was conserved but that ribonucleoprotein complex formation required higher PCBP2 and 3CD\n            <jats:sup>pro<\/jats:sup>\n            concentrations, depending on the size of the deletion. Overall, this study confirmed the characteristics of persistent CVB3 infection observed in heart tissues and provided a possible explanation for the low level of RNA replication observed for the 5\u2032-deleted viral genomes\u2014a less stable ribonucleoprotein complex formed with proteins involved in viral RNA replication.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Dilated cardiomyopathy is the most common indication for heart transplantation worldwide, and coxsackie B viruses are detected in about one-third of idiopathic dilated cardiomyopathies. Terminal deletions at the 5\u2032 end of the viral genome involving an RNA secondary structure required for RNA replication have been recently reported as a possible mechanism of virus persistence in the human heart. These mutations are likely to disrupt the correct folding of an RNA secondary structure required for viral RNA replication. In this report, we demonstrate that transfected RNAs harboring 5\u2032-terminal sequence deletions are able to direct the synthesis of viral proteins, but not genomic RNAs, in human and murine cardiomyocytes. Moreover, we show that the binding of cellular and viral replication factors to viral RNA is conserved despite genomic deletions but that the impaired RNA synthesis associated with terminally deleted viruses could be due to destabilization of the ribonucleoprotein complexes formed.\n          <\/jats:p>","DOI":"10.1128\/jvi.00423-17","type":"journal-article","created":{"date-parts":[[2017,5,25]],"date-time":"2017-05-25T00:40:15Z","timestamp":1495672815000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":36,"title":["Functional Consequences of RNA 5\u2032-Terminal Deletions on Coxsackievirus B3 RNA Replication and Ribonucleoprotein Complex Formation"],"prefix":"10.1128","volume":"91","author":[{"given":"Nicolas","family":"L\u00e9v\u00eaque","sequence":"first","affiliation":[{"name":"EA-4684 CardioVir, Faculty of Medicine and University Hospital Center, University of Reims Champagne-Ardenne, Reims, France"},{"name":"Center for Virus Research and Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magali","family":"Garcia","sequence":"additional","affiliation":[{"name":"EA-4331 LITEC, Faculty of Medicine and Pharmacy, University of Poitiers, Poitiers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Bouin","sequence":"additional","affiliation":[{"name":"Center for Virus Research and Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph H. 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