SARS-CoV-2 infects and replicates in cells of the human endocrine and exocrine pancreas
SARS-CoV-2 infects and replicates in cells of the human endocrine and exocrine pancreas
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DOI：
10.1038/s42255-021-00347-1
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发表时间：
2021-02-03
影响因子：
20.8
通讯作者：
Kleger, Alexander
中科院分区：
文献类型：
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作者：
Mueller, Janis A.;Gross, Ruediger;Kleger, Alexander
与糖尿病相关的糖尿病可能是病毒相关的β细胞破坏的结果。临床数据表明，引起2019冠状病毒病（COVID-19）的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）会损害葡萄糖稳态，但缺乏SARS-CoV-2可以感染胰腺组织的实验证据。在本研究中，我们表明，SARS-CoV-2感染细胞的人外分泌和内分泌胰腺离体和体内。我们证明了人类β细胞表达病毒进入蛋白，并且SARS-CoV-2在培养的人类胰岛中感染和复制。感染与形态、转录和功能变化相关，包括β细胞中胰岛素分泌颗粒数量减少和葡萄糖刺激的胰岛素分泌受损。在COVID-19全身尸检中，我们在胰腺外分泌细胞中检测到SARS-CoV-2核衣壳蛋白，并在所有四名受试患者的β细胞标记物NKX6.1染色阳性且靠近胰岛的细胞中检测到SARS-CoV-2核衣壳蛋白。我们的数据确定了人类胰腺作为SARS-CoV-2感染的靶点，并表明β细胞感染可能有助于在COVID-19患者中观察到的代谢失调。SARS-CoV-2被证明在人类胰腺组织中感染和复制，包括在β细胞中，这与形态学，转录组学和功能变化有关。
Infection-related diabetes can arise as a result of virus-associated beta-cell destruction. Clinical data suggest that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the coronavirus disease 2019 (COVID-19), impairs glucose homoeostasis, but experimental evidence that SARS-CoV-2 can infect pancreatic tissue has been lacking. In the present study, we show that SARS-CoV-2 infects cells of the human exocrine and endocrine pancreas ex vivo and in vivo. We demonstrate that human beta-cells express viral entry proteins, and SARS-CoV-2 infects and replicates in cultured human islets. Infection is associated with morphological, transcriptional and functional changes, including reduced numbers of insulin-secretory granules in beta-cells and impaired glucose-stimulated insulin secretion. In COVID-19 full-body postmortem examinations, we detected SARS-CoV-2 nucleocapsid protein in pancreatic exocrine cells, and in cells that stain positive for the beta-cell marker NKX6.1 and are in close proximity to the islets of Langerhans in all four patients investigated. Our data identify the human pancreas as a target of SARS-CoV-2 infection and suggest that beta-cell infection could contribute to the metabolic dysregulation observed in patients with COVID-19.SARS-CoV-2 is shown to infect and replicate in human pancreatic tissue, including in beta-cells, which is associated with morphological, transcriptomic and functional changes.