{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T13:26:07Z","timestamp":1790429167046,"version":"4.1.0"},"reference-count":34,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,2,20]],"date-time":"2020-02-20T00:00:00Z","timestamp":1582156800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK104166, UC4104218, U01 DK104218, R01 AI116920"],"award-info":[{"award-number":["DK104166, UC4104218, U01 DK104218, R01 AI116920"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Enteroviral infections are implicated in islet autoimmunity and type 1 diabetes (T1D) pathogenesis. Significant \u03b2-cell stress and damage occur with viral infection, leading to cells that are dysfunctional and vulnerable to destruction. Human stem cell-derived \u03b2 (SC-\u03b2) cells are insulin-producing cell clusters that closely resemble native \u03b2 cells. To better understand the events precipitated by enteroviral infection of \u03b2 cells, we investigated transcriptional and proteomic changes in SC-\u03b2 cells challenged with coxsackie B virus (CVB). We confirmed infection by demonstrating that viral protein colocalized with insulin-positive SC-\u03b2 cells by immunostaining. Transcriptome analysis showed a decrease in insulin gene expression following infection, and combined transcriptional and proteomic analysis revealed activation of innate immune pathways, including type I interferon (IFN), IFN-stimulated genes, nuclear factor-kappa B (NF-\u03baB) and downstream inflammatory cytokines, and major histocompatibility complex (MHC) class I. Finally, insulin release by CVB4-infected SC-\u03b2 cells was impaired. These transcriptional, proteomic, and functional findings are in agreement with responses in primary human islets infected with CVB ex vivo. Human SC-\u03b2 cells may serve as a surrogate for primary human islets in virus-induced diabetes models. Because human SC-\u03b2 cells are more genetically tractable and accessible than primary islets, they may provide a preferred platform for investigating T1D pathogenesis and developing new treatments.<\/jats:p>","DOI":"10.3390\/microorganisms8020295","type":"journal-article","created":{"date-parts":[[2020,2,21]],"date-time":"2020-02-21T08:59:47Z","timestamp":1582275587000},"page":"295","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Proteomic and Transcriptional Profiles of Human Stem Cell-Derived \u03b2 Cells Following Enteroviral Challenge"],"prefix":"10.3390","volume":"8","author":[{"given":"Julius O.","family":"Nyalwidhe","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Cell Biology and Leroy T. Canoles Jr. Cancer Research Center, Eastern Virginia Medical School, Norfolk, VA 23501, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata","family":"Jurczyk","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basanthi","family":"Satish","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1462-2022","authenticated-orcid":false,"given":"Sambra","family":"Redick","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha","family":"Qaisar","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie I.","family":"Trombly","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4000-7891","authenticated-orcid":false,"given":"Pranitha","family":"Vangala","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Racicot","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Bortell","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Harlan","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale L.","family":"Greiner","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Brehm","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry L.","family":"Nadler","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Cell Biology and Leroy T. Canoles Jr. Cancer Research Center, Eastern Virginia Medical School, Norfolk, VA 23501, USA"},{"name":"Department of Medicine and Pharmacology, New York Medical College, Valhalla, NY 10595, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2556-9100","authenticated-orcid":false,"given":"Jennifer P.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,20]]},"reference":[{"key":"ref_1","first-page":"149","article-title":"Viruses and type 1 diabetes: A new look at an old story","volume":"14","author":"Craig","year":"2013","journal-title":"Pediatric Diabetes"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"d35","DOI":"10.1136\/bmj.d35","article-title":"Enterovirus infection and type 1 diabetes mellitus: Systematic review and meta-analysis of observational molecular studies","volume":"342","author":"Yeung","year":"2011","journal-title":"BMJ"},{"key":"ref_3","doi-asserted-by":"crossref","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":"ref_4","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1038\/ng1800","article-title":"A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region","volume":"38","author":"Smyth","year":"2006","journal-title":"Nat. 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