{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:11:48Z","timestamp":1792451508673,"version":"4.5.0"},"reference-count":244,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,7,3]],"date-time":"2020-07-03T00:00:00Z","timestamp":1593734400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"NIGMS","doi-asserted-by":"publisher","award":["GM109780"],"award-info":[{"award-number":["GM109780"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK099550"],"award-info":[{"award-number":["DK099550"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Type 1 diabetes (T1D) is a polygenic autoimmune disease characterized by immune-mediated destruction of insulin-producing \u03b2-cells. The concordance rate for T1D in monozygotic twins is \u224830\u201350%, indicating that environmental factors also play a role in T1D development. Previous studies have demonstrated that enterovirus infections such as coxsackievirus type B (CVB) are associated with triggering T1D. Prior to autoantibody development in T1D, viral RNA and antibodies against CVB can be detected within the blood, stool, and pancreata. An innate pathogen recognition receptor, melanoma differentiation-associated protein 5 (MDA5), which is encoded by the IFIH1 gene, has been associated with T1D onset. It is unclear how single nucleotide polymorphisms in IFIH1 alter the structure and function of MDA5 that may lead to exacerbated antiviral responses contributing to increased T1D-susceptibility. Binding of viral dsRNA via MDA5 induces synthesis of antiviral proteins such as interferon-alpha and -beta (IFN-\u03b1\/\u03b2). Viral infection and subsequent IFN-\u03b1\/\u03b2 synthesis can lead to ER stress within insulin-producing \u03b2-cells causing neo-epitope generation, activation of \u03b2-cell-specific autoreactive T cells, and \u03b2-cell destruction. Therefore, an interplay between genetics, enteroviral infections, and antiviral responses may be critical for T1D development.<\/jats:p>","DOI":"10.3390\/microorganisms8070993","type":"journal-article","created":{"date-parts":[[2020,7,3]],"date-time":"2020-07-03T06:51:20Z","timestamp":1593759080000},"page":"993","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Innate Viral Sensor MDA5 and Coxsackievirus Interplay in Type 1 Diabetes Development"],"prefix":"10.3390","volume":"8","author":[{"given":"Samuel I.","family":"Blum","sequence":"first","affiliation":[{"name":"Department of Microbiology, Comprehensive Diabetes Center, The University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5861-7597","authenticated-orcid":false,"given":"Hubert M.","family":"Tse","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Comprehensive Diabetes Center, The University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1038\/nature08933","article-title":"Genetics, pathogenesis and clinical interventions in type 1 diabetes","volume":"464","author":"Bluestone","year":"2010","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2094","DOI":"10.2337\/db15-1690","article-title":"Type 1 Diabetes Genetic Risk Score: A Novel Tool to Discriminate Monogenic and Type 1 Diabetes","volume":"65","author":"Patel","year":"2016","journal-title":"Diabetes"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Rogers, M.A.M., Kim, C., Banerjee, T., and Lee, J.M. 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