National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan, China.
State Key Laboratory of Medical Molecular Biology, Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Medical Primate Research Center, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.
Signal Transduct Target Ther. 2021 Apr 24;6(1):169. doi: 10.1038/s41392-021-00591-7.
Neurological manifestations are frequently reported in the COVID-19 patients. Neuromechanism of SARS-CoV-2 remains to be elucidated. In this study, we explored the mechanisms of SARS-CoV-2 neurotropism via our established non-human primate model of COVID-19. In rhesus monkey, SARS-CoV-2 invades the CNS primarily via the olfactory bulb. Thereafter, viruses rapidly spread to functional areas of the central nervous system, such as hippocampus, thalamus, and medulla oblongata. The infection of SARS-CoV-2 induces the inflammation possibly by targeting neurons, microglia, and astrocytes in the CNS. Consistently, SARS-CoV-2 infects neuro-derived SK-N-SH, glial-derived U251, and brain microvascular endothelial cells in vitro. To our knowledge, this is the first experimental evidence of SARS-CoV-2 neuroinvasion in the NHP model, which provides important insights into the CNS-related pathogenesis of SARS-CoV-2.
在 COVID-19 患者中经常报告出现神经系统表现。SARS-CoV-2 的神经发病机制仍有待阐明。在这项研究中，我们通过已建立的 COVID-19 非人类灵长类动物模型探索了 SARS-CoV-2 嗜神经性的机制。在恒河猴中，SARS-CoV-2 主要通过嗅球侵入中枢神经系统。此后，病毒迅速传播到中枢神经系统的功能区域，如海马体、丘脑和延髓。SARS-CoV-2 的感染可能通过靶向中枢神经系统中的神经元、小胶质细胞和星形胶质细胞引发炎症。一致地，SARS-CoV-2 感染体外来源的 SK-N-SH、胶质来源的 U251 和脑微血管内皮细胞。据我们所知，这是非人类灵长类动物模型中 SARS-CoV-2 神经入侵的第一个实验证据，为 SARS-CoV-2 与中枢神经系统相关的发病机制提供了重要的见解。
