McMahon Courtney L, Staples Hilary, Gazi Michal, Carrion Ricardo, Hsieh Jenny
Department of Biology, University of Texas at San Antonio, San Antonio, TX 78249, USA; Brain Health Consortium, University of Texas at San Antonio, San Antonio, TX 78249, USA.
Texas Biomedical Research Institute, San Antonio, TX 78227, USA.
Stem Cell Reports. 2021 May 11;16(5):1156-1164. doi: 10.1016/j.stemcr.2021.01.016.
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.
2019年冠状病毒病（COVID-19）患者已表现出多种神经并发症，关于严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的嗜神经性仍有许多有待揭示之处。人干细胞衍生的脑类器官为研究SARS-CoV-2对大脑的细胞效应提供了一种有价值的体外方法。在此，我们使用人胚胎干细胞衍生的皮质类器官来研究SARS-CoV-2是否能在体外感染脑组织，发现皮质类器官在低病毒滴度下且在6小时内即可被感染。重要的是，我们表明在我们的模型中，神经胶质细胞和脉络丛细胞是优先被靶向的细胞，而神经元则未被靶向。有趣的是，我们还在SARS-CoV-2感染的细胞中发现了血管紧张素转换酶2的表达；然而，并未发生涉及DNA片段化的病毒复制和细胞死亡。我们认为我们的模型是一个易于操作的平台，可用于研究SARS-CoV-2感染脑组织的细胞效应。
