Journal Article

SARS-CoV-2 productively infects human brain microvascular endothelial cells

Chen, Huan-Chun, Zhang, Yu-Fei, Li, Liang, Jin, Mei-Lin, Wang, Xiang-Ru, Zhang, Hui-Peng, Yang, Rui-Cheng, Huang, Kun, Tan, Chen

2022

Overview

Background The emergence of the novel, pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global health emergency. SARS-CoV-2 is highly contagious and has a high mortality rate in severe patients. However, there is very limited information on the effect of SARS-CoV-2 infection on the integrity of the blood–brain barrier (BBB). Methods RNA-sequencing profiling was performed to analyze the transcriptomic changes in human brain microvascular endothelial cells (hBMECs) after SARS-CoV-2 infection. Bioinformatic tools were used for differential analysis. Immunofluorescence, real-time quantitative PCR, and Western blotting analysis were used to explore biological phenotypes. Results A total of 927 differentially expressed genes were identified, 610 of which were significantly upregulated while the remaining 317 were downregulated. We verified the significant induction of cytokines, chemokines, and adhesion molecules in hBMECs by SARS-CoV-2, suggesting an activation of the vascular endothelium in brain. Moreover, we demonstrated that SARS-CoV-2 infection could increase the BBB permeability, by downregulating as well as remodeling the intercellular tight junction proteins. Conclusions Our findings demonstrated that SARS-CoV-2 infection can cause BBB dysfunction, providing novel insights into the understanding of SARS-CoV-2 neuropathogenesis. Moreover, this finding shall constitute a new approach for future prevention and treatment of SARS-CoV-2-induced CNS infection.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Amino acids / Analysis / Annotations / Biomedical and Life Sciences / Biomedicine / Blood-brain barrier / Brain / Care and treatment / Cell adhesion & migration / Chemokines / Coronaviruses / COVID-19 / Cytokines / Diagnosis / Endothelial cells / Endothelium / Experiments / Genes / Genomes / Health aspects / Human brain microvascular endothelial cells / Immune response / Immunofluorescence / Immunology / Infections / Inflammatory response / Laboratory animals / Measurement / Membrane permeability / Microvasculature / Neurobiology / Neurologic manifestations of general diseases / Neurology / Neuropathogenesis / Neurosciences / Permeability / Phenotypes / Proteins / Public health / Risk factors / SARS-CoV-2 / Severe acute respiratory syndrome coronavirus 2 / Transcriptomics / Viruses / Western blotting