PDF(Pubmed)
Abstract：
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with neurological sequelae including haemorrhage, thrombosis and ischaemic necrosis and encephalitis. However, the mechanism by which this occurs is unclear. Neurological disease associated with COVID-19 has been proposed to occur following direct infection of the central nervous system and/or indirectly by local or systemic immune activation. We evaluated the expression of angiotensin-converting enzyme-2 and transmembrane protease, serine 2 (TMPRSS2) in brain tissue from five healthy human donors and observed low-level expression of these proteins in cells morphologically consistent with astrocytes, neurons and choroidal ependymal cells within the frontal cortex and medulla oblongata. Primary human astrocytes, neurons, choroid plexus epithelial cells and pericytes supported productive SARS-CoV-2 infection with ancestral, Alpha, Delta and Omicron variants. Infected cells supported the full viral life cycle, releasing infectious virus particles. In contrast, primary brain microvascular endothelial cells and microglia were refractory to SARS-CoV-2 infection. These data support a model whereby SARS-CoV-2 can infect human brain cells, and the mechanism of viral entry warrants further investigation.
摘要：
严重急性呼吸综合征冠状病毒-2（SARS-CoV-2）感染与包括出血在内的神经系统后遗症有关，血栓形成和缺血性坏死和脑炎。然而,发生这种情况的机制尚不清楚。有人提出，与COVID-19相关的神经系统疾病是在中枢神经系统直接感染后和/或通过局部或全身免疫激活间接感染后发生的。我们评估了血管紧张素转换酶2和跨膜蛋白酶的表达，来自五个健康人类供体的脑组织中的丝氨酸2（TMPRSS2），并观察到这些蛋白在形态学上与星形胶质细胞一致的细胞中的低水平表达，额叶皮质和延髓内的神经元和脉络膜室管膜细胞。原代人星形胶质细胞,神经元，脉络丛上皮细胞和周细胞支持祖先的生产性SARS-CoV-2感染，阿尔法,Delta和Omicron变体。感染的细胞支持完整的病毒生命周期，释放感染性病毒颗粒。相比之下,原发性脑微血管内皮细胞和小胶质细胞对SARS-CoV-2感染难治。这些数据支持SARS-CoV-2可以感染人类脑细胞的模型，病毒进入的机制值得进一步研究。
