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Open AccessArticle

Proteomic and Transcriptional Profiles of Human Stem Cell-Derived β Cells Following Enteroviral Challenge

1
Department of Microbiology and Molecular Cell Biology and Leroy T. Canoles Jr. Cancer Research Center, Eastern Virginia Medical School, Norfolk, VA 23501, USA
2
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA
3
Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA
4
Department of Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA
5
Department of Medicine and Pharmacology, New York Medical College, Valhalla, NY 10595, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this paper.
Microorganisms 2020, 8(2), 295; https://doi.org/10.3390/microorganisms8020295
Received: 9 January 2020 / Revised: 14 February 2020 / Accepted: 18 February 2020 / Published: 20 February 2020
(This article belongs to the Special Issue Enterovirus and Type 1 Diabetes)
Enteroviral infections are implicated in islet autoimmunity and type 1 diabetes (T1D) pathogenesis. Significant β-cell stress and damage occur with viral infection, leading to cells that are dysfunctional and vulnerable to destruction. Human stem cell-derived β (SC-β) cells are insulin-producing cell clusters that closely resemble native β cells. To better understand the events precipitated by enteroviral infection of β cells, we investigated transcriptional and proteomic changes in SC-β cells challenged with coxsackie B virus (CVB). We confirmed infection by demonstrating that viral protein colocalized with insulin-positive SC-β 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-κB) and downstream inflammatory cytokines, and major histocompatibility complex (MHC) class I. Finally, insulin release by CVB4-infected SC-β 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-β cells may serve as a surrogate for primary human islets in virus-induced diabetes models. Because human SC-β cells are more genetically tractable and accessible than primary islets, they may provide a preferred platform for investigating T1D pathogenesis and developing new treatments. View Full-Text
Keywords: coxsackie B virus; beta cells; type 1 diabetes coxsackie B virus; beta cells; type 1 diabetes
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Nyalwidhe, J.O.; Jurczyk, A.; Satish, B.; Redick, S.; Qaisar, N.; Trombly, M.I.; Vangala, P.; Racicot, R.; Bortell, R.; Harlan, D.M.; Greiner, D.L.; Brehm, M.A.; Nadler, J.L.; Wang, J.P. Proteomic and Transcriptional Profiles of Human Stem Cell-Derived β Cells Following Enteroviral Challenge. Microorganisms 2020, 8, 295.

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