The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) readily infects a variety of cell types impacting the function of vital organ systems, with particularly severe impact on respiratory function. It proves fatal for one percent of those infected. Neurological symptoms, which range in severity, accompany a significant proportion of COVID-19 cases, indicating a potential vulnerability of neural cell types. To assess whether human cortical cells can be directly infected by SARS-CoV-2, we utilized primary human cortical tissue and stem cell-derived cortical organoids. We find significant and predominant infection in cortical astrocytes in both primary and organoid cultures, with minimal infection of other cortical populations. Infected astrocytes had a corresponding increase in reactivity characteristics, growth factor signaling, and cellular stress. Although human cortical cells, including astrocytes, have minimal ACE2 expression, we find high levels of alternative coronavirus receptors in infected astrocytes, including DPP4 and CD147. Inhibition of DPP4 reduced infection and decreased expression of the cell stress marker, ARCN1. We find tropism of SARS-CoV-2 for human astrocytes mediated by DPP4, resulting in reactive gliosis-type injury.

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SARS-CoV-2 对开发人类皮质星形胶质细胞的趋向性

严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 很容易感染影响重要器官系统功能的多种细胞类型，对呼吸功能的影响尤其严重。它被证明对百分之一的感染者是致命的。严重程度不同的神经系统症状伴随着很大比例的 COVID-19 病例，表明神经细胞类型存在潜在的脆弱性。为了评估人类皮质细胞是否可以被 SARS-CoV-2 直接感染，我们利用了原代人类皮质组织和干细胞衍生的皮质类器官。我们在原代和类器官培养物中发现皮质星形胶质细胞显着且主要的感染，而其他皮质种群的感染最小。受感染的星形胶质细胞在反应性特征、生长因子信号、和细胞压力。尽管包括星形胶质细胞在内的人类皮层细胞的 ACE2 表达最少，但我们在受感染的星形胶质细胞中发现了高水平的替代冠状病毒受体，包括 DPP4 和 CD147。抑制 DPP4 可减少感染并降低细胞应激标志物 ARCN1 的表达。我们发现 SARS-CoV-2 对 DPP4 介导的人星形胶质细胞的趋向性，导致反应性神经胶质增生型损伤。