{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:49:45Z","timestamp":1790866185406,"version":"4.1.0"},"reference-count":56,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T00:00:00Z","timestamp":1754092800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disorder characterized by the destruction of insulin-producing pancreatic beta cells, resulting in lifelong insulin dependence. While genetic susceptibility\u2014particularly human leukocyte antigen (HLA) class II alleles\u2014is a major risk factor, accumulating evidence implicates viral infections as potential environmental triggers in disease onset and progression. This narrative review synthesizes current findings on the role of viral pathogens in T1DM pathogenesis. Enteroviruses, especially Coxsackie B strains, are the most extensively studied and show strong epidemiological and mechanistic associations with beta-cell autoimmunity. Large prospective studies\u2014including Diabetes Virus Detection (DiViD), The environmental determinans of diabetes in the young (TEDDY), Milj\u00f8faktorer i utvikling av type 1 diabetes (MIDIA), and Diabetes Autoimmunity Study in the Young (DAISY)\u2014consistently demonstrate correlations between enteroviral presence and the initiation or acceleration of islet autoimmunity. Other viruses\u2014such as mumps, rubella, rotavirus, influenza A (H1N1), and SARS-CoV-2\u2014have been investigated for their potential involvement through direct cytotoxic effects, immune activation, or molecular mimicry. Interestingly, certain viruses like varicella-zoster virus (VZV) and cytomegalovirus (CMV) may exert modulatory or even protective influences on disease progression. Proposed mechanisms include direct beta-cell infection, molecular mimicry, bystander immune activation, and dysregulation of innate and adaptive immunity. Although definitive causality remains unconfirmed, the complex interplay between genetic predisposition, immune responses, and viral exposure underscores the need for further mechanistic research. Elucidating these pathways may inform future strategies for targeted prevention, early detection, and vaccine or antiviral development in at-risk populations.<\/jats:p>","DOI":"10.3390\/biology14080981","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T10:58:26Z","timestamp":1754564306000},"page":"981","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["The Role of Viral Infections in the Immunopathogenesis of Type 1 Diabetes Mellitus: A Narrative Review"],"prefix":"10.3390","volume":"14","author":[{"given":"Ioanna","family":"Kotsiri","sequence":"first","affiliation":[{"name":"Second Department of Internal Medicine, Asklepieion General Hospital Voulas, 16673 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Xanthi","sequence":"additional","affiliation":[{"name":"Second Department of Internal Medicine, General Hospital Tzaneio, 18537 Pireas, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charalampia-Melangeli","family":"Domazinaki","sequence":"additional","affiliation":[{"name":"Second Department of Internal Medicine, Asklepieion General Hospital Voulas, 16673 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8883-7275","authenticated-orcid":false,"given":"Emmanouil","family":"Magiorkinis","sequence":"additional","affiliation":[{"name":"Department of Laboratory Haematology, Metaxas Anticancer Memorial Hospital, 18537 Pireas, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","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":"ref_2","doi-asserted-by":"crossref","unstructured":"(2007). 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