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Expression of SARS-CoV-2-related receptors in cells of the neurovascular unit: implications for HIV-1 infection

Authors
  • Torices, Silvia1
  • Cabrera, Rosalba1
  • Stangis, Michael1
  • Naranjo, Oandy1
  • Fattakhov, Nikolai1
  • Teglas, Timea1
  • Adesse, Daniel2
  • Toborek, Michal1
  • 1 University of Miami Miller School of Medicine, 528E Gautier Bldg. 1011 NW 15th Street, Miami, FL, 33136, USA , Miami (United States)
  • 2 Instituto Oswaldo Cruz, Fiocruz, CEP, Rio de Janeiro, RJ, 21045-900, Brazil , Rio de Janeiro (Brazil)
Type
Published Article
Journal
Journal of Neuroinflammation
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Jul 29, 2021
Volume
18
Issue
1
Identifiers
DOI: 10.1186/s12974-021-02210-2
Source
Springer Nature
Keywords
Disciplines
  • Research
License
Green

Abstract

BackgroundNeurological complications are common in patients affected by COVID-19 due to the ability of SARS-CoV-2 to infect brains. While the mechanisms of this process are not fully understood, it has been proposed that SARS-CoV-2 can infect the cells of the neurovascular unit (NVU), which form the blood-brain barrier (BBB). The aim of the current study was to analyze the expression pattern of the main SARS-CoV-2 receptors in naïve and HIV-1-infected cells of the NVU in order to elucidate a possible pathway of the virus entry into the brain and a potential modulatory impact of HIV-1 in this process.MethodsThe gene and protein expression profile of ACE2, TMPRSS2, ADAM17, BSG, DPP4, AGTR2, ANPEP, cathepsin B, and cathepsin L was assessed by qPCR, immunoblotting, and immunostaining, respectively. In addition, we investigated if brain endothelial cells can be affected by the exposure to the S1 subunit of the S protein, the domain responsible for the direct binding of SARS-CoV-2 to the ACE2 receptors.ResultsThe receptors involved in SARS-CoV-2 infection are co-expressed in the cells of the NVU, especially in astrocytes and microglial cells. These receptors are functionally active as exposure of endothelial cells to the SARS CoV-2 S1 protein subunit altered the expression pattern of tight junction proteins, such as claudin-5 and ZO-1. Additionally, HIV-1 infection upregulated ACE2 and TMPRSS2 expression in brain astrocytes and microglia cells.ConclusionsThese findings provide key insight into SARS-CoV-2 recognition by cells of the NVU and may help to develop possible treatment of CNS complications of COVID-19.

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