Cargando…

Coxsackievirus-Induced Proteomic Alterations in Primary Human Islets Provide Insights for the Etiology of Diabetes

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 coxsac...

Descripción completa

Detalles Bibliográficos
Autores principales: Nyalwidhe, Julius O., Gallagher, Glen R., Glenn, Lindsey M., Morris, Margaret A., Vangala, Pranitha, Jurczyk, Agata, Bortell, Rita, Harlan, David M., Wang, Jennifer P., Nadler, Jerry L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Endocrine Society 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5686651/
https://www.ncbi.nlm.nih.gov/pubmed/29264452
http://dx.doi.org/10.1210/js.2017-00278
_version_ 1783278815991037952
author Nyalwidhe, Julius O.
Gallagher, Glen R.
Glenn, Lindsey M.
Morris, Margaret A.
Vangala, Pranitha
Jurczyk, Agata
Bortell, Rita
Harlan, David M.
Wang, Jennifer P.
Nadler, Jerry L.
author_facet Nyalwidhe, Julius O.
Gallagher, Glen R.
Glenn, Lindsey M.
Morris, Margaret A.
Vangala, Pranitha
Jurczyk, Agata
Bortell, Rita
Harlan, David M.
Wang, Jennifer P.
Nadler, Jerry L.
author_sort Nyalwidhe, Julius O.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5686651
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Endocrine Society
record_format MEDLINE/PubMed
spelling pubmed-56866512017-12-20 Coxsackievirus-Induced Proteomic Alterations in Primary Human Islets Provide Insights for the Etiology of Diabetes Nyalwidhe, Julius O. Gallagher, Glen R. Glenn, Lindsey M. Morris, Margaret A. Vangala, Pranitha Jurczyk, Agata Bortell, Rita Harlan, David M. Wang, Jennifer P. Nadler, Jerry L. J Endocr Soc Research Articles 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. Endocrine Society 2017-09-11 /pmc/articles/PMC5686651/ /pubmed/29264452 http://dx.doi.org/10.1210/js.2017-00278 Text en Copyright © 2017 Endocrine Society https://creativecommons.org/licenses/by-nc-nd/4.0/ This article has been published under the terms of the Creative Commons Attribution Non-Commercial, No-Derivatives License (CC BY-NC-ND; https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Articles
Nyalwidhe, Julius O.
Gallagher, Glen R.
Glenn, Lindsey M.
Morris, Margaret A.
Vangala, Pranitha
Jurczyk, Agata
Bortell, Rita
Harlan, David M.
Wang, Jennifer P.
Nadler, Jerry L.
Coxsackievirus-Induced Proteomic Alterations in Primary Human Islets Provide Insights for the Etiology of Diabetes
title Coxsackievirus-Induced Proteomic Alterations in Primary Human Islets Provide Insights for the Etiology of Diabetes
title_full Coxsackievirus-Induced Proteomic Alterations in Primary Human Islets Provide Insights for the Etiology of Diabetes
title_fullStr Coxsackievirus-Induced Proteomic Alterations in Primary Human Islets Provide Insights for the Etiology of Diabetes
title_full_unstemmed Coxsackievirus-Induced Proteomic Alterations in Primary Human Islets Provide Insights for the Etiology of Diabetes
title_short Coxsackievirus-Induced Proteomic Alterations in Primary Human Islets Provide Insights for the Etiology of Diabetes
title_sort coxsackievirus-induced proteomic alterations in primary human islets provide insights for the etiology of diabetes
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5686651/
https://www.ncbi.nlm.nih.gov/pubmed/29264452
http://dx.doi.org/10.1210/js.2017-00278
work_keys_str_mv AT nyalwidhejuliuso coxsackievirusinducedproteomicalterationsinprimaryhumanisletsprovideinsightsfortheetiologyofdiabetes
AT gallagherglenr coxsackievirusinducedproteomicalterationsinprimaryhumanisletsprovideinsightsfortheetiologyofdiabetes
AT glennlindseym coxsackievirusinducedproteomicalterationsinprimaryhumanisletsprovideinsightsfortheetiologyofdiabetes
AT morrismargareta coxsackievirusinducedproteomicalterationsinprimaryhumanisletsprovideinsightsfortheetiologyofdiabetes
AT vangalapranitha coxsackievirusinducedproteomicalterationsinprimaryhumanisletsprovideinsightsfortheetiologyofdiabetes
AT jurczykagata coxsackievirusinducedproteomicalterationsinprimaryhumanisletsprovideinsightsfortheetiologyofdiabetes
AT bortellrita coxsackievirusinducedproteomicalterationsinprimaryhumanisletsprovideinsightsfortheetiologyofdiabetes
AT harlandavidm coxsackievirusinducedproteomicalterationsinprimaryhumanisletsprovideinsightsfortheetiologyofdiabetes
AT wangjenniferp coxsackievirusinducedproteomicalterationsinprimaryhumanisletsprovideinsightsfortheetiologyofdiabetes
AT nadlerjerryl coxsackievirusinducedproteomicalterationsinprimaryhumanisletsprovideinsightsfortheetiologyofdiabetes