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 |
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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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