Department of Medicine; Department of Bioinformatics and Integrative Biology; Program in Molecular Medicine
Endocrine System Diseases | Endocrinology | Endocrinology, Diabetes, and Metabolism | Immune System Diseases | Immunology and Infectious Disease | Nutritional and Metabolic Diseases
Enteroviral infections have been associated with the development of type 1 diabetes (T1D), a chronic inflammatory disease characterized by autoimmune destruction of insulin-producing pancreatic beta cells. Cultured human islets, including the insulin-producing beta cells, can be infected with coxsackievirus B4 (CVB4) and thus are useful for understanding cellular responses to infection. We performed quantitative mass spectrometry analysis on cultured primary human islets infected with CVB4 to identify molecules and pathways altered upon infection. Corresponding uninfected controls were included in the study for comparative protein expression analyses. Proteins were significantly and differentially regulated in human islets challenged with virus compared with their uninfected counterparts. Complementary analyses of gene transcripts in CVB4-infected primary islets over a time course validated the induction of RNA transcripts for many of the proteins that were increased in the proteomics studies. Notably, infection with CVB4 results in a considerable decrease in insulin. Genes/proteins modulated during CVB4 infection also include those involved in activation of immune responses, including type I interferon pathways linked to T1D pathogenesis and with antiviral, cell repair, and inflammatory properties. Our study applies proteomics analyses to cultured human islets challenged with virus and identifies target proteins that could be useful in T1D interventions.
coxsackievirus, immune response, inflammation, innate immunity, insulin, mass spectrometry, pancreatic islets, proteomics, type 1 diabetes
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Copyright © 2017 Endocrine Society. This article has been published under the terms of the Creative Commons Attribution NonCommercial, No-Derivatives License (CC BY-NC-ND; https://creativecommons.org/licenses/by-ncnd/4.0/)
DOI of Published Version
J Endocr Soc. 2017 Sep 11;1(10):1272-1286. doi: 10.1210/js.2017-00278. eCollection 2017 Oct 1. Link to article on publisher's site
Journal of the Endocrine Society
Nyalwidhe JO, Gallagher GR, Glenn LM, Morris MA, Vangala P, Jurczyk A, Bortell R, Harlan DM, Wang JP, Nadler JL. (2017). Coxsackievirus-Induced Proteomic Alterations in Primary Human Islets Provide Insights for the Etiology of Diabetes. Open Access Articles. https://doi.org/10.1210/js.2017-00278. Retrieved from https://escholarship.umassmed.edu/oapubs/3261
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
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