The SARS-CoV-2 envelope protein disrupts barrier function in an in vitro human blood-brain barrier model

Ju, Jiahang and Su, Yuwen and Zhou, You and Wei, Hui and Xu, Qi (2022) The SARS-CoV-2 envelope protein disrupts barrier function in an in vitro human blood-brain barrier model. Frontiers in Cellular Neuroscience, 16. ISSN 1662-5102

[thumbnail of fncel.2022.897564] Text
fncel.2022.897564 - Published Version

Download (3kB)

Abstract

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 in vitro 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.

Item Type: Article
Subjects: Institute Archives > Medical Science
Depositing User: Managing Editor
Date Deposited: 30 Mar 2023 05:51
Last Modified: 05 Feb 2024 04:20
URI: http://eprint.subtopublish.com/id/eprint/1948

Actions (login required)

View Item
View Item