小柯机器人

美国希望之城贝克曼研究所Yanhong Shi、加州大学旧金山分校Vaithilingaraja Arumugaswami等研究人员合作揭示ApoE亚型依赖性的SARS-CoV-2神经向性和细胞反应。相关论文于2020年12月29日在线发表在《细胞—干细胞》杂志上。

研究人员在人诱导的多能干细胞（hiPSC）模型中测试了SARS-CoV2的神经向性，并观察到神经元和星形胶质细胞的共培养和类器官增强了神经元和星形胶质细胞的低度感染。然后，研究人员生成了等基因的ApoE3/3和ApoE4/4 hiPSC，并发现ApoE4/4神经元和星形胶质细胞中SARS-CoV-2感染的比率增加。SARS-CoV-2感染后，ApoE4星形胶质细胞显示出增大的大小和核碎裂升高。

最后，研究人员表明瑞德西韦治疗可预防hiPSC神经元和星形胶质细胞的SARS-CoV2感染。这些发现表明，ApoE4可能在COVID-19严重性中起因果作用。了解危险因素如何影响COVID-19的敏感性和严重性将有助于人们了解不同患者人群的潜在长期影响。

据悉，ApoE4是阿尔茨海默氏病的重要遗传风险因素，与严重COVID-19的风险增加有关。但是，ApoE4是否会改变COVID-19的敏感性或严重性，并且直接病毒感染在脑细胞中的作用仍然不清楚。

附：英文原文

Title: ApoE isoform-dependent SARS-CoV-2 neurotropism and cellular response

Author: Cheng Wang, Mingzi Zhang, Gustavo Garcia, E. Tian, Qi Cui, Xianwei Chen, Guihua Sun, Jinghui Wang, Vaithilingaraja Arumugaswami, Yanhong Shi

Issue&Volume: 2020-12-29

Abstract: ApoE4, a strong genetic risk factor for Alzheimer’s disease, has been associated with increased risk for severe COVID-19. However, it is unclear whether ApoE4 alters COVID-19 susceptibility or severity and the role of direct viral infection in brain cells remains obscure. We tested the neurotropism of SARS-CoV2 in human induced pluripotent stem cell (hiPSC) models and observed low-grade infection of neurons and astrocytes that is boosted in neuron-astrocyte co-cultures and organoids. We then generated isogenic ApoE3/3 and ApoE4/4 hiPSCs and found an increased rate of SARS-CoV-2 infection in ApoE4/4 neurons and astrocytes. ApoE4 astrocytes exhibited enlarged size and elevated nuclear fragmentation upon SARS-CoV-2 infection. Finally, we show that remdesivir treatment prevents SARS-CoV2 infection of hiPSC-neurons and astrocytes. These findings suggest that ApoE4 may play a causal role in COVID-19 severity. Understanding how risk factors impact COVID-19 susceptibility and severity will help us understand potential long-term effects in different patient populations.

DOI: 10.1016/j.stem.2020.12.018

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30602-0

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