SARS-CoV-2 Infectivity and Neurological Targets in the Brain
SARS-CoV-2 Infectivity and Neurological Targets in the Brain
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DOI：
10.1007/s10571-020-00947-7
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发表时间：
2020-08-25
影响因子：
4
通讯作者：
Hill, James M.
中科院分区：
文献类型：
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作者：
Lukiw, Walter J.;Pogue, Aileen;Hill, James M.
新型严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）入侵人类宿主细胞的通道是通过多种免疫和非免疫细胞类型中表达的血管紧张素转换酶2 （ACE2）跨膜受体。引起2019冠状病毒病（COVID-19; CoV-19）的SARS-CoV-2具有不同寻常的能力，可以通过新的不依赖网格蛋白和小泡的内吞途径同时攻击许多不同类型的人类宿主细胞，对多种细胞、组织和器官系统造成伤害，并利用宿主的任何免疫弱点。这种多管齐下的攻击在一定程度上解释了在covid -19患者中观察到的严重程度和广泛多样的体征和症状。为了进一步了解SARS-CoV-2感染的机制和途径，以及特定细胞和组织类型和器官系统对SARS-CoV-2攻击的易感性，我们分析了85个人体组织中ACE2的表达，包括21个不同的大脑区域，7个胎儿组织和8个对照。ACE2除在呼吸、消化、肾排泄和生殖细胞中表达强烈外，在杏仁核、大脑皮层和脑干中也有高表达。ACE2在脑干的脑桥和延髓中表达水平最高，这可能在一定程度上解释了许多covid -19患者对严重呼吸窘迫的易感性。
The gateway for invasion by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into human host cells is via the angiotensin-converting enzyme 2 (ACE2) transmembrane receptor expressed in multiple immune and nonimmune cell types. SARS-CoV-2, that causes coronavirus disease 2019 (COVID-19; CoV-19) has the unusual capacity to attack many different types of human host cells simultaneously via novel clathrin- and caveolae-independent endocytic pathways, becoming injurious to diverse cells, tissues and organ systems and exploiting any immune weakness in the host. The elicitation of this multipronged attack explains in part the severity and extensive variety of signs and symptoms observed in CoV-19 patients. To further our understanding of the mechanism and pathways of SARS-CoV-2 infection and susceptibility of specific cell- and tissue-types and organ systems to SARS-CoV-2 attack in this communication we analyzed ACE2 expression in 85 human tissues including 21 different brain regions, 7 fetal tissues and 8 controls. Besides strong ACE2 expression in respiratory, digestive, renal-excretory and reproductive cells, high ACE2 expression was also found in the amygdala, cerebral cortex and brainstem. The highest ACE2 expression level was found in the pons and medulla oblongata in the human brainstem, containing the medullary respiratory centers of the brain, and may in part explain the susceptibility of many CoV-19 patients to severe respiratory distress.