{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T01:38:37Z","timestamp":1760233117885,"version":"build-2065373602"},"reference-count":39,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T00:00:00Z","timestamp":1670889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003100","name":"F\u00e9d\u00e9ration fran\u00e7aise de cardiologie","doi-asserted-by":"publisher","award":["2019"],"award-info":[{"award-number":["2019"]}],"id":[{"id":"10.13039\/501100003100","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Reims Champagne Ardenne","award":["2019"],"award-info":[{"award-number":["2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Emergence of 5\u2032 terminally deleted coxsackievirus-B RNA forms (CVB-TD) have been associated with the development of human diseases. These CVB-TD RNA forms have been detected in mouse pancreas during acute or persistent experimental infections. To date, the impact of the replication activities of CVB-TD RNA forms on insulin metabolism remains unexplored. Using an immunocompetent mouse model of CVB3\/28 infection, acute and persistent infections of major CVB-TD populations were evidenced in the pancreas. The inoculation of mice with homogenized pancreases containing major CVB-TD populations induced acute and chronic pancreatic infections with pancreatitis. In the mouse pancreas, viral capsid protein 1 (VP1) expression colocalized with a decrease in beta cells insulin content. Moreover, in infected mouse pancreases, we showed a decrease in pro-hormone convertase 2 (PCSK2) mRNA, associated with a decrease in insulin plasmatic concentration. Finally, transfection of synthetic CVB-TD50 RNA forms into cultured rodent pancreatic beta cells demonstrated that viral replication with protein synthesis activities decreased the PCSK2 mRNA expression levels, impairing insulin secretion. In conclusion, our results show that the emergence and maintenance of major CVB-TD RNA replicative forms in pancreatic beta cells can play a direct, key role in the pathophysiological mechanisms leading to the development of type 1 diabetes.<\/jats:p>","DOI":"10.3390\/v14122781","type":"journal-article","created":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T02:22:41Z","timestamp":1670984561000},"page":"2781","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Replication Activities of Major 5\u2032 Terminally Deleted Group-B Coxsackievirus RNA Forms Decrease PCSK2 mRNA Expression Impairing Insulin Maturation in Pancreatic Beta Cells"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2443-1684","authenticated-orcid":false,"given":"Domitille","family":"Callon","sequence":"first","affiliation":[{"name":"Cardiovir EA-4684, Faculty of Medicine, University of Reims Champagne Ardennes, 51 Rue Cognacq Jay, 51097 Reims, France"},{"name":"Pathology Department, Academic Hospital of Reims, Robert Debr\u00e9, 51100 Reims, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aur\u00e9lien","family":"Guedra","sequence":"additional","affiliation":[{"name":"Cardiovir EA-4684, Faculty of Medicine, University of Reims Champagne Ardennes, 51 Rue Cognacq Jay, 51097 Reims, France"},{"name":"Pathology Department, Academic Hospital of Reims, Robert Debr\u00e9, 51100 Reims, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne-Laure","family":"Lebreil","sequence":"additional","affiliation":[{"name":"Cardiovir EA-4684, Faculty of Medicine, University of Reims Champagne Ardennes, 51 Rue Cognacq Jay, 51097 Reims, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laetitia","family":"Heng","sequence":"additional","affiliation":[{"name":"Cardiovir EA-4684, Faculty of Medicine, University of Reims Champagne Ardennes, 51 Rue Cognacq Jay, 51097 Reims, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Bouland","sequence":"additional","affiliation":[{"name":"Pathology Department, Academic Hospital of Reims, Robert Debr\u00e9, 51100 Reims, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Forn\u00e8s","sequence":"additional","affiliation":[{"name":"Cardiovir EA-4684, Faculty of Medicine, University of Reims Champagne Ardennes, 51 Rue Cognacq Jay, 51097 Reims, France"},{"name":"Pathology Department, Academic Hospital of Reims, Robert Debr\u00e9, 51100 Reims, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1717-4667","authenticated-orcid":false,"given":"Fatma","family":"Berri","sequence":"additional","affiliation":[{"name":"Cardiovir EA-4684, Faculty of Medicine, University of Reims Champagne Ardennes, 51 Rue Cognacq Jay, 51097 Reims, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurent","family":"Andreoletti","sequence":"additional","affiliation":[{"name":"Cardiovir EA-4684, Faculty of Medicine, University of Reims Champagne Ardennes, 51 Rue Cognacq Jay, 51097 Reims, France"},{"name":"Virology Department, Academic Hospital of Reims, Robert Debr\u00e9, 51100 Reims, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Akhbari, P., Richardson, S.J., and Morgan, N.G. 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