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
Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, Virginia 23501.
Leroy T. Canoles Jr. Cancer Research Center, Eastern Virginia Medical School, Norfolk, Virginia 23501.
J Endocr Soc. 2017 Sep 11;1(10):1272-1286. doi: 10.1210/js.2017-00278. eCollection 2017 Oct 1.
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.
肠道病毒感染与1型糖尿病（T1D）的发生有关，1型糖尿病是一种慢性炎症性疾病，其特征是产生胰岛素的胰腺β细胞发生自身免疫性破坏。包括产生胰岛素的β细胞在内的培养的人胰岛可被柯萨奇病毒B4（CVB4）感染，因此有助于了解细胞对感染的反应。我们对感染CVB4的培养原代人胰岛进行了定量质谱分析，以鉴定感染后改变的分子和途径。研究中纳入了相应的未感染对照进行比较蛋白质表达分析。与未感染的胰岛相比，受到病毒攻击的人胰岛中的蛋白质受到显著且差异的调节。对CVB4感染的原代胰岛在一段时间内的基因转录本进行的补充分析证实了蛋白质组学研究中许多增加的蛋白质的RNA转录本的诱导。值得注意的是，感染CVB4会导致胰岛素显著减少。CVB4感染期间调节的基因/蛋白质还包括那些参与免疫反应激活的基因/蛋白质，包括与T1D发病机制相关的I型干扰素途径以及具有抗病毒、细胞修复和炎症特性的途径。我们的研究将蛋白质组学分析应用于受到病毒攻击的培养人胰岛，并鉴定出可能对T1D干预有用的靶蛋白。
