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

Autor: Nikolai Fattakhov, Rosalba Cabrera, Michael Stangis, Timea Teglas, Oandy Naranjo, Michal Toborek, Daniel Adesse, Silvia Torices
Rok vydání: 2021
Předmět:
0301 basic medicine
ACE2
HIV Infections
Virus Replication
Cathepsin B
Cathepsin L
0302 clinical medicine
Receptor
Cells
Cultured
Blood-brain barrier
Neurons
Brain Diseases
Tight junction
Microglia
General Neuroscience
Cell biology
medicine.anatomical_structure
Neurology
Receptors
Virus
Angiotensin-Converting Enzyme 2
Protein subunit
Primary Cell Culture
Immunology
Biology
Blood–brain barrier
Receptor
Angiotensin
Type 2
Article
03 medical and health sciences
Cellular and Molecular Neuroscience
Downregulation and upregulation
Viral entry
medicine
Humans
RC346-429
TMPRSS2
SARS-CoV-2
Research
fungi
COVID-19
030104 developmental biology
Cell culture
Astrocytes
HIV-1
biology.protein
Blood Vessels
Neurology. Diseases of the nervous system
Endothelium
Vascular
Nervous System Diseases
030217 neurology & neurosurgery
Zdroj: Research Square
article-version (status) pre
article-version (number) 1
Journal of Neuroinflammation
Journal of Neuroinflammation, Vol 18, Iss 1, Pp 1-16 (2021)
ISSN: 1742-2094
Popis: 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.
Databáze: OpenAIRE
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