SARS-CoV-2 targets glial cells in human cortical organoids.
SARS-CoV-2 targets glial cells in human cortical organoids.
复制标题
SARS-COV-2靶向人类皮质器官中的神经胶质细胞。
DOI：
10.1016/j.stemcr.2021.01.016
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发表时间：
2021-05-11
影响因子：
5.9
通讯作者：
Hsieh J
中科院分区：
文献类型：
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作者：
McMahon CL;Staples H;Gazi M;Carrion R;Hsieh J
2019冠状病毒病（COVID-19）患者表现出多种神经系统并发症，关于严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）的嗜神经性仍有很多有待揭示。人类干细胞衍生的脑类器官为研究SARS-CoV-2对大脑的细胞影响提供了一种有价值的体外方法。在这里，我们使用人类胚胎干细胞衍生的皮质类器官来研究SARS-CoV-2是否可以在体外感染脑组织，发现皮质类器官可以在低病毒滴度和6小时内感染。重要的是，我们发现在我们的模型中，神经胶质细胞和脉络膜丛细胞是优先靶向的，而不是神经元。有趣的是，我们还在SARS-CoV-2感染细胞中发现了血管紧张素转换酶2的表达；然而，不会发生涉及DNA断裂的病毒复制和细胞死亡。我们认为，我们的模型是一个易于处理的平台，可以研究SARS-CoV-2感染在脑组织中的细胞效应。SARS-CoV-2在感染后4天内不会发生复制SARS-CoV-2在体外优先靶向胶质细胞和脉络丛细胞在感染后14天内与SARS-CoV-2在细胞内共定位。研究发现，SARS-CoV-2可以以低病毒载量感染这些类器官，但在感染后4天内不会复制。具体来说，SARS-CoV-2在该模型中优先靶向神经胶质细胞和脉络膜丛细胞。
Coronavirus disease 2019 (COVID-19) patients have manifested a variety of neurological complications, and there is still much to reveal regarding the neurotropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human stem cell-derived brain organoids offer a valuable in vitro approach to study the cellular effects of SARS-CoV-2 on the brain. Here we used human embryonic stem cell-derived cortical organoids to investigate whether SARS-CoV-2 could infect brain tissue in vitro and found that cortical organoids could be infected at low viral titers and within 6 h. Importantly, we show that glial cells and cells of the choroid plexus were preferentially targeted in our model, but not neurons. Interestingly, we also found expression of angiotensin-converting enzyme 2 in SARS-CoV-2 infected cells; however, viral replication and cell death involving DNA fragmentation does not occur. We believe that our model is a tractable platform to study the cellular effects of SARS-CoV-2 infection in brain tissue. SARS-CoV-2 infects human cortical organoids at low viral loads within 6 h Replication of SARS-CoV-2 does not occur within 4 days post infection SARS-CoV-2 preferentially targets glia and choroid plexus cells in vitro Cleaved caspase-3 co-localizes with SARS-CoV-2 in cells at 14 days post infection In this article, Hsieh and colleagues investigated the neurotropism of the virus responsible for COVID-19, SARS-CoV-2. Using human ESC-derived brain organoids, this study found that SARS-CoV-2 can infect these organoids at low viral loads, but does not replicate within 4 days post infection. Specifically, SARS-CoV-2 preferentially targeted glial cells and cells of the choroid plexus in this model.
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通讯作者：
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