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SARS-CoV-2可感染人脑类器官中的脑脉络丛
作者:小柯机器人 发布时间:2020/10/15 15:41:15

英国MRC分子生物学实验室Madeline A. Lancaster团队发现,SARS-CoV-2感染脑脉络丛并破坏人脑类器官中的血液-脑脊液屏障。该项研究成果于2020年10月13日在线发表在《细胞—干细胞》杂志上。

研究人员使用人类多能干细胞衍生的大脑类器官来检查SARS-CoV-2神经嗜性。研究人员发现在表达丰富脂蛋白的成熟脉络丛细胞中表达病毒受体ACE2,但在神经元或其他细胞类型中却没有。研究人员用SARS-CoV-2突刺伪病毒和活病毒感染类器官,来证明了脉络丛上皮细胞的病毒趋向性,但几乎没有感染神经元或神经胶质。研究人员发现被感染的细胞是脉络丛上皮屏障的载脂蛋白和ACE2表达细胞。
 
最后,研究人员表明SARS-CoV-2感染会损害脉络丛上皮,导致穿过这一重要屏障发生泄漏,该屏障通常会阻止病原体、免疫细胞和细胞因子进入脑脊液和大脑。
 
据悉,SARS-CoV-2病毒引起的COVID-19导致呼吸道症状可能致命。但是,在某些患者中也观察到神经系统症状。这些并发症的原因目前未知。
 
附:英文原文

Title: SARS-CoV-2 infects the brain choroid plexus and disrupts the blood-CSF-barrier in human brain organoids

Author: Laura Pellegrini, Anna Albecka, Donna L. Mallery, Max J. Kellner, David Paul, Andrew P. Carter, Leo C. James, Madeline A. Lancaster

Issue&Volume: 2020-10-13

Abstract: Coronavirus disease-19 (COVID-19), caused by the SARS-CoV-2 virus, leads to respiratory symptoms that can be fatal. However, neurological symptoms have also been observed in some patients. The cause of these complications is currently unknown. Here, we use human pluripotent stem cell-derived brain organoids to examine SARS-CoV-2 neurotropism. We find expression of viral receptor ACE2 in mature choroid plexus cells expressing abundant lipoproteins, but not in neurons or other cell types. We challenge organoids with SARS-CoV-2 spike pseudovirus and live virus to demonstrate viral tropism for choroid plexus epithelial cells, but little to no infection of neurons or glia. We find that infected cells are apolipoprotein and ACE2 expressing cells of the choroid plexus epithelial barrier. Finally, we show that infection with SARS-CoV-2 damages the choroid plexus epithelium, leading to leakage across this important barrier that normally prevents entry of pathogens, immune cells and cytokines into cerebrospinal fluid and the brain.

DOI: 10.1016/j.stem.2020.10.001

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30495-1

期刊信息

Cell Stem Cell:《细胞—干细胞》,创刊于2007年。隶属于细胞出版社,最新IF:21.464
官方网址:https://www.cell.com/cell-stem-cell/home
投稿链接:https://www.editorialmanager.com/cell-stem-cell/default.aspx