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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Coxsackie B4 virus infection of β cells and natural killer cell insulitis in recent-onset type 1 diabetic patients
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Coxsackie B4 virus infection of β cells and natural killer cell insulitis in recent-onset type 1 diabetic patients

机译：柯萨奇B4病毒感染新发1型糖尿病患者的β细胞和自然杀伤细胞性岛炎

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摘要

Type 1 diabetes is characterized by T cell-mediated autoimmune destruction of pancreatic β cells. Several studies have suggested an association between Coxsackie enterovirus seroconversion and onset of disease. However, a direct link between β cell viral infection and islet inflammation has not been established. We analyzed pancreatic tissue from six type 1 diabetic and 26 control organ donors. Immunohistochemical, electron microscopy, whole-genome ex vivo nucleotide sequencing, cell culture, and immuno-logical studies demonstrated Coxsackie B4 enterovirus in specimens from three of the six diabetic patients. Infection was specific of β cells, which showed nondestructive islet inflammation mediated mainly by natural killer cells. Islets from enterovirus-positive samples displayed reduced insulin secretion in response to glucose and other secretagogues. In addition, virus extracted from positive islets was able to infect β cells from human islets of nondiabetic donors, causing viral inclusions and signs of pyknosis. None of the control organ donors showed signs of viral infection. These studies provide direct evidence that enterovirus can infect β cells in patients with type 1 diabetes and that infection is associated with inflammation and functional impairment.
机译：1型糖尿病的特征是胰腺T细胞介导的T细胞介导的自身免疫破坏。多项研究表明，柯萨奇肠病毒血清转化与疾病发作之间存在关联。然而，β细胞病毒感染与胰岛炎症之间没有直接联系。我们分析了六位1型糖尿病患者和26位对照器官供体的胰腺组织。免疫组织化学，电子显微镜，全基因组离体核苷酸测序，细胞培养和免疫学研究表明，在六名糖尿病患者中的三名患者的标本中出现了柯萨奇B4肠病毒。感染是β细胞特有的，表现出主要由自然杀伤细胞介导的非破坏性胰岛炎症。肠道病毒阳性样本的胰岛对葡萄糖和其他促分泌素的反应显示胰岛素分泌减少。此外，从阳性胰岛中提取的病毒能够感染非糖尿病供者的人类胰岛中的β细胞，从而导致病毒包涵体和缩现象。对照器官供体均未显示病毒感染迹象。这些研究提供了直接的证据，证明肠病毒可以感染1型糖尿病患者的β细胞，并且感染与炎症和功能受损有关。

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