Deleterious Effects of SARS-CoV-2 Infection on Human Pancreatic Cells.
Deleterious Effects of SARS-CoV-2 Infection on Human Pancreatic Cells.
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DOI：
10.3389/fcimb.2021.678482
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发表时间：
2021
影响因子：
5.7
通讯作者：
Sareen D
中科院分区：
文献类型：
--
作者：
Shaharuddin SH;Wang V;Santos RS;Gross A;Wang Y;Jawanda H;Zhang Y;Hasan W;Garcia G Jr;Arumugaswami V;Sareen D
COVID-19大流行已感染全球超过1. 54亿人，并造成超过320万人死亡。它由严重急性呼吸道综合征冠状病毒2型（SARS-CoV-2）传播，影响呼吸道以及表达病毒进入受体血管紧张素转换酶2（ACE 2）受体的肺外系统，包括胰腺。重要的是，内分泌和外分泌胰腺（后者由导管和腺泡细胞组成）表达高水平的ACE 2，这与在某些COVID-19病例中观察到的以急性胰腺炎为特征的功能受损相关。由于急性胰腺炎已经是美国住院治疗的最常见胃肠道原因之一，并且大多数研究SARS-CoV-2对胰腺影响的研究都是临床和观察性的，因此我们利用人类iPSC技术来研究SARS-CoV-2感染对含有内分泌和外分泌细胞的iPSC衍生胰腺培养物的潜在有害影响。有趣的是，iPSC衍生的胰腺培养物允许SARS-CoV-2进入并建立感染，从而扰乱其正常的分子和细胞表型。感染增加了一种关键的细胞因子，CXCL 12，已知参与胰腺的炎症反应。对感染的胰腺培养物的转录组分析证实，SARS-CoV-2劫持了这些细胞中的核糖体机制。值得注意的是，胰腺的SARS-CoV-2感染性在COVID-19患者的死后组织中得到了证实，这表明SARS-CoV-2在胰腺内分泌和外分泌细胞中共定位，并增加了一些胰腺导管应激反应基因的表达。因此，我们证明了SARS-CoV-2可以直接感染人iPSC衍生的胰腺细胞，并有强有力的证据支持该病毒存在于确诊的COVID-19人类病例的死后胰腺组织中。这种新的iPSC衍生的胰腺培养模型将为理解SARS-CoV-2感染开辟新的途径，并可能建立一个内分泌和外分泌胰腺特异性抗病毒药物筛选的平台。
COVID-19 pandemic has infected more than 154 million people worldwide and caused more than 3.2 million deaths. It is transmitted by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and affects the respiratory tract as well as extra-pulmonary systems, including the pancreas, that express the virus entry receptor, Angiotensin-Converting Enzyme 2 (ACE2) receptor. Importantly, the endocrine and exocrine pancreas, the latter composed of ductal and acinar cells, express high levels of ACE2, which correlates to impaired functionality characterized as acute pancreatitis observed in some cases presenting with COVID-19. Since acute pancreatitis is already one of the most frequent gastrointestinal causes of hospitalization in the U.S. and the majority of studies investigating the effects of SARS-CoV-2 on the pancreas are clinical and observational, we utilized human iPSC technology to investigate the potential deleterious effects of SARS-CoV-2 infection on iPSC-derived pancreatic cultures containing endocrine and exocrine cells. Interestingly, iPSC-derived pancreatic cultures allow SARS-CoV-2 entry and establish infection, thus perturbing their normal molecular and cellular phenotypes. The infection increased a key cytokine, CXCL12, known to be involved in inflammatory responses in the pancreas. Transcriptome analysis of infected pancreatic cultures confirmed that SARS-CoV-2 hijacks the ribosomal machinery in these cells. Notably, the SARS-CoV-2 infectivity of the pancreas was confirmed in post-mortem tissues from COVID-19 patients, which showed co-localization of SARS-CoV-2 in pancreatic endocrine and exocrine cells and increased the expression of some pancreatic ductal stress response genes. Thus, we demonstrate that SARS-CoV-2 can directly infect human iPSC-derived pancreatic cells with strong supporting evidence of presence of the virus in post-mortem pancreatic tissue of confirmed COVID-19 human cases. This novel model of iPSC-derived pancreatic cultures will open new avenues for the comprehension of the SARS-CoV-2 infection and potentially establish a platform for endocrine and exocrine pancreas-specific antiviral drug screening.
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DOI：
10.1038/s41575-020-00389-y
发表时间：
2021-01
期刊：
Nature reviews. Gastroenterology & hepatology
影响因子：
--
作者：
de-Madaria E;Capurso G
通讯作者：
Capurso G
影响因子：
4.6
作者：
Kosti I;Jain N;Aran D;Butte AJ;Sirota M
通讯作者：
Sirota M
影响因子：
5.4
作者：
Chen, CJ;Makino, S
通讯作者：
Makino, S
影响因子：
5.4
作者：
Dove, B;Brooks, G;Hiscox, JA
通讯作者：
Hiscox, JA
影响因子：
44.5
作者：
Holman, Naomi;Knighton, Peter;Valabhji, Jonathan
通讯作者：
Valabhji, Jonathan