{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T18:51:24Z","timestamp":1793299884873,"version":"4.5.0"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T00:00:00Z","timestamp":1734480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Type 1 diabetes (T1D) is characterized by a prolonged autoimmune attack resulting in the massive loss of insulin-producing beta cells. The initiation and progression of T1D depends on a complex interaction between genetic, immunological and environmental factors. Epidemiological, experimental and clinical evidence suggest a link between viral infections, particularly Coxsackievirus type B (CVB), and T1D development. Specifically, infections by the CVB serotype 1 (CVB1) contribute to the triggering of autoimmunity against beta cells in genetically predisposed individuals, and prolonged and probably non-lytic infections by CVB are associated with the development of T1D. However, the molecular mechanisms underlying CVB1 replication and establishing persistent infections in human pancreatic beta cells remain poorly understood. Here we show that the N6-methyladenosine (m6A) RNA epigenetic modification machinery regulates CVB1 amplification in the human beta cells. Using small interfering RNA (siRNA) targeting m6A writers and erasers, we observed that downregulation of m6A writers increases CVB1 amplification, while the downregulation of m6A erasers decreases it. Notably, the inhibition of Fat Mass and Obesity-associated protein (FTO), a key m6A eraser, reduced by 95% the production of infectious CVB1 in both human insulin-producing EndoC-\u03b2H1 cells and in induced pluripotent stem cell (iPSC)-derived islets. The FTO inhibitor reduced CVB1 expression within 6\u202fh post-infection, suggesting a direct regulation of the CVB1 genome by m6A modification. Furthermore, in the absence of viral replication, FTO inhibition also decreased the translation of the incoming CVB1 genome, indicating that m6A plays a critical role in the initial stages of viral RNA translation. In addition, modulation of the m6A machinery affected the type I interferon response after poly-IC transfection, a mimic of RNA virus replication, but did not affect the cellular antiviral response in CVB1-infected cells. Altogether, these observations suggest that m6A directly affects CVB1 production. Our study provides the first evidence that the m6A epigenetic modification machinery controls CVB amplification in human pancreatic beta cells. This suggests that the m6A machinery is a potential target to control CVB infection in T1D and raises the possibility of an epigenetic control in the establishment of persistent CVB infections observed in the pancreas in individuals with type 1 diabetes.<\/jats:p>","DOI":"10.3389\/fmicb.2024.1501061","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T06:47:45Z","timestamp":1734504465000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["The N6-methyladenosine RNA epigenetic modification modulates the amplification of coxsackievirus B1 in human pancreatic beta cells"],"prefix":"10.3389","volume":"15","author":[{"given":"Maressa Fernandes","family":"Bonfim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Aitchedji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flore","family":"Van Goethem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lionel","family":"Sauvage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thibault","family":"Poinsot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Calonne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Deplus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Fuks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Decio L.","family":"Eizirik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Op de Beeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,12,18]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1080\/19382014.2021.1948282","article-title":"A functional genomic approach to identify reference genes for human pancreatic beta cell real-time quantitative RT-PCR analysis","volume":"13","author":"Alvelos","year":"2021","journal-title":"Islets"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"eabd6527","DOI":"10.1126\/sciadv.abd6527","article-title":"Islet expression of type I interferon response sensors is associated with immune infiltration and viral infection in type 1 diabetes","volume":"7","author":"Apaolaza","year":"2021","journal-title":"Sci. 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Biol."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"768","DOI":"10.3390\/microorganisms10040768","article-title":"Fighting Enteroviral infections to prevent type 1 diabetes","volume":"10","author":"Nekoua","year":"2022","journal-title":"Microorganisms"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/S2213-8587(19)30412-7","article-title":"Type 1 diabetes\u2014early life origins and changing epidemiology","volume":"8","author":"Norris","year":"2020","journal-title":"Lancet Diab. Endocrinol."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"687","DOI":"10.2337\/db11-1157","article-title":"Type 1 diabetes is associated with enterovirus infection in gut mucosa","volume":"61","author":"Oikarinen","year":"2012","journal-title":"Diabetes"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"2491","DOI":"10.1007\/s00125-021-05525-0","article-title":"Characterisation of enterovirus Rna detected in the pancreas and other specimens of live patients with newly diagnosed type 1 diabetes in the DiViD study","volume":"64","author":"Oikarinen","year":"2021","journal-title":"Diabetologia"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1006\/cyto.1998.0426","article-title":"Quantification of murine cytokine mrnas using real time quantitative reverse transcriptase Pcr","volume":"11","author":"Overbergh","year":"1999","journal-title":"Cytokine"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1007\/s00125-018-4763-3","article-title":"Trends and cyclical variation in the incidence of childhood type 1 diabetes in 26 European centres in the 25 year period 1989-2013: a multicentre prospective registration study","volume":"62","author":"Patterson","year":"2019","journal-title":"Diabetologia"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"127","DOI":"10.3390\/v16010127","article-title":"Functional impacts of Epitranscriptomic m(6)a modification on Hiv-1 infection","volume":"16","author":"Phillips","year":"2024","journal-title":"Viruses"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1038\/cr.2014.3","article-title":"Mammalian Wtap is a regulatory subunit of the Rna N6-methyladenosine methyltransferase","volume":"24","author":"Ping","year":"2014","journal-title":"Cell Res."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"e3001683","DOI":"10.1371\/journal.pbio.3001683","article-title":"Alternative splicing of Mettl3 explains apparently Mettl3-independent m6A modifications in mrna","volume":"20","author":"Poh","year":"2022","journal-title":"PLoS Biol."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"1582","DOI":"10.1038\/s41467-021-21904-y","article-title":"N(6)-methyladenosine Rna modification suppresses antiviral innate sensing pathways via reshaping double-stranded Rna","volume":"12","author":"Qiu","year":"2021","journal-title":"Nat. Commun."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"3589","DOI":"10.1172\/JCI58447","article-title":"A genetically engineered human pancreatic beta cell line exhibiting glucose-inducible insulin secretion","volume":"121","author":"Ravassard","year":"2011","journal-title":"J. Clin. Invest."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1007\/s12022-014-9297-8","article-title":"Pancreatic pathology in type 1 diabetes mellitus","volume":"25","author":"Richardson","year":"2014","journal-title":"Endocr. Pathol."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.1007\/s00125-009-1276-0","article-title":"The prevalence of enteroviral capsid protein vp1 immunostaining in pancreatic islets in human type 1 diabetes","volume":"52","author":"Richardson","year":"2009","journal-title":"Diabetologia"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"e00997","DOI":"10.1128\/jvi.00997-22","article-title":"Wtap targets the Mettl3 m6A-methyltransferase complex to cytoplasmic hepatitis C virus RNA to regulate infection","volume":"96","author":"Sacco","year":"2022","journal-title":"J. Virol."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1007\/7651_2015_291","article-title":"Pancreatic Beta cell survival and signaling pathways: effects of type 1 diabetes-associated genetic variants","volume":"1433","author":"Santin","year":"2016","journal-title":"Methods Mol. 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