Article
Expression of SARS-CoV-2-related receptors in cells of the neurovascular unit: implications for HIV-1 infection
Registro en:
TORICES, Silvia et al. Expression of SARS-CoV-2-related receptors in cells of the neurovascular unit: implications for HIV-1 infection. Journal of Neuroinflamation, v.18, n. 167, 16 p, 2021.
1742-2094
10.1186/s12974-021-02210-2
Autor
Torices, Silvia
Cabrera, Rosalba
Stangis, Michael
Naranjo, Oaindy
Fattakhov, Nikolai
Teglas, Timea
Adesse, Daniel
Toborek, Michal
Resumen
Background: Neurological 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.
Methods: The 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.
Results: The 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.
Conclusions: These 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.