Wu Bingshan, Wang Weihong, Wang Haopeng, Zou Quanli, Hu Benxia, Ye Lei, Hu Yangchun, Xie Yuhuan, Huang Nali, Lan Qing, Cheng Hongwei, Dong Jun, Dai Xingliang
Department of Neurosurgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Lab of Single Cell, Sinotech Genomics Co., Ltd., Shanghai, China.
Front Oncol. 2020 Nov 16;10:566599. doi: 10.3389/fonc.2020.566599. eCollection 2020.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the recent global COVID-19 outbreak, which led to a public health emergency. Entry of SARS-CoV-2 into human cells is dependent on the SARS-CoV receptor, angiotensin converting enzyme 2 (ACE2) receptor, and cathepsin. Cathepsin degrades the spike protein (S protein), which results in the entry of viral nucleic acid into the human host cell.
We explored the susceptibility of the central nervous system (CNS) to SARS-CoV-2 infection using single-cell transcriptome analysis of glioblastoma.
The results showed that ACE2 expression is relatively high in endothelial cells (ECs), bone marrow mesenchymal stem cells (BMSCs), and neural precursor cells (NPCs). Cathepsin B (Cat B) and cathepsin (Cat L) were also strongly expressed in various cell clusters within the glioblastoma microenvironment. Immunofluorescence staining of glioma and normal brain tissue chips further confirmed that ACE2 expression co-localized with CD31, CD73, and nestin, which confirmed the susceptibility to SARS-CoV-2 of nervous system cells, including ECs, BMSCs, and NPCs, from clinical specimens.
These findings reveal the mechanism of SARS-CoV-2 neural invasion and suggest that special attention should be paid to SARS-CoV-2-infected patients with neural symptoms, especially those who suffered a glioma.
严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引发了近期全球新冠疫情,导致公共卫生紧急事件。SARS-CoV-2进入人体细胞依赖于SARS-CoV受体、血管紧张素转换酶2(ACE2)受体和组织蛋白酶。组织蛋白酶可降解刺突蛋白(S蛋白),从而使病毒核酸进入人类宿主细胞。
我们通过对胶质母细胞瘤进行单细胞转录组分析,探究中枢神经系统(CNS)对SARS-CoV-2感染的易感性。
结果显示,ACE2在内皮细胞(ECs)、骨髓间充质干细胞(BMSCs)和神经前体细胞(NPCs)中表达相对较高。组织蛋白酶B(Cat B)和组织蛋白酶L(Cat L)在胶质母细胞瘤微环境中的各种细胞簇中也有强烈表达。胶质瘤和正常脑组织芯片的免疫荧光染色进一步证实,ACE2表达与CD31、CD73和巢蛋白共定位,这从临床标本中证实了包括ECs、BMSCs和NPCs在内的神经细胞对SARS-CoV-2的易感性。
这些发现揭示了SARS-CoV-2神经侵袭的机制,并表明应特别关注出现神经症状的SARS-CoV-2感染患者,尤其是患有胶质瘤的患者。