Ju Jiahang, Su Yuwen, Zhou You, Wei Hui, Xu Qi
State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.
Neuroscience Center, Chinese Academy of Medical Sciences, Beijing, China.
Front Cell Neurosci. 2022 Aug 23;16:897564. doi: 10.3389/fncel.2022.897564. eCollection 2022.
Patients with coronavirus disease 2019 (COVID-19) have been frequently reported to exhibit neurological manifestations and disruption of the blood-brain barrier (BBB). Among the risk factors for BBB breakdown, the loss of endothelial cells and pericytes has caused widespread concern. Recent studies have revealed that severe acute respiratory syndrome coronavirus 2 envelope (S2E) protein caused cell death. We tested the hypothesis that the S2E protein alone could induce BBB dysfunction. The S2E protein bound to human BBB-related cells and inhibited cell viability in a dose- and time-dependent manner. Importantly, the S2E protein disrupted barrier function in an BBB model composed of HCMEC/D3 (brain endothelial cell line), HBVP (brain vascular pericyte), and U87MG (astrocyte cell line) cells and suppressed the expression of major genes involved in maintaining endothelial permeability and function. In addition, the S2E protein crossed the HCMEC/D3 monolayer. The S2E protein triggered inflammatory responses in HCMEC/D3 and U87MG cells. Taken together, these results show for the first time that the S2E protein has a negative impact on the BBB. Therapies targeting the S2E protein could protect against and treat central nervous system manifestations in COVID-19 patients.
2019年冠状病毒病（COVID-19）患者经常被报道出现神经学表现和血脑屏障（BBB）破坏。在血脑屏障破坏的风险因素中，内皮细胞和周细胞的丧失引起了广泛关注。最近的研究表明，严重急性呼吸综合征冠状病毒2包膜（S2E）蛋白会导致细胞死亡。我们检验了仅S2E蛋白就能诱导血脑屏障功能障碍的假说。S2E蛋白与人血脑屏障相关细胞结合，并以剂量和时间依赖性方式抑制细胞活力。重要的是，S2E蛋白在由HCMEC/D3（脑内皮细胞系）、HBVP（脑血管周细胞）和U87MG（星形胶质细胞系）细胞组成的血脑屏障模型中破坏屏障功能，并抑制参与维持内皮通透性和功能的主要基因的表达。此外，S2E蛋白穿过了HCMEC/D3单层细胞。S2E蛋白在HCMEC/D3和U87MG细胞中引发炎症反应。综上所述，这些结果首次表明S2E蛋白对血脑屏障有负面影响。针对S2E蛋白的疗法可以预防和治疗COVID-19患者的中枢神经系统表现。
