Coxsackievirus-Induced Proteomic Alterations in Primary Human Islets Provide Insights for the Etiology of Diabetes
AuthorsNyalwidhe, Julius O.
Gallagher, Glen R.
Glenn, Lindsey M.
Morris, Margaret A.
Harlan, David M.
Wang, Jennifer P.
Nadler, Jerry L.
UMass Chan AffiliationsProgram in Molecular Medicine
Department of Bioinformatics and Integrative Biology
Department of Medicine
Document TypeJournal Article
type 1 diabetes
Endocrine System Diseases
Endocrinology, Diabetes, and Metabolism
Immune System Diseases
Immunology and Infectious Disease
Nutritional and Metabolic Diseases
MetadataShow full item record
AbstractEnteroviral 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.
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
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/40457
RightsCopyright © 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/)
Except where otherwise noted, this item's license is described as 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/)