Comparison of SARS-CoV-2 Receptors Expression in Primary Endothelial Cells and Retinoic Acid-Differentiated Human Neuronal Cells

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is primarily responsible for coronavirus disease (COVID-19) and it is characterized by respiratory illness with fever and dyspnea. Severe vascular problems and several other manifestations, including neurological ones, have also been frequ...

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Autores principales:	Francesca Benedetti, Giovannino Silvestri, Carla Mavian, Matthew Weichseldorfer, Arshi Munawwar, Melanie N. Cash, Melissa Dulcey, Amy Y. Vittor, Massimo Ciccozzi, Marco Salemi, Olga S. Latinovic, Davide Zella
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	SARS-CoV-2 ACE-2 SARS-receptors neuronal cells endothelial cells Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/78fbba028c134778ab3f1da872855fd0
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spelling	oai:doaj.org-article:78fbba028c134778ab3f1da872855fd02021-11-25T19:13:13ZComparison of SARS-CoV-2 Receptors Expression in Primary Endothelial Cells and Retinoic Acid-Differentiated Human Neuronal Cells10.3390/v131121931999-4915https://doaj.org/article/78fbba028c134778ab3f1da872855fd02021-10-01T00:00:00Zhttps://www.mdpi.com/1999-4915/13/11/2193https://doaj.org/toc/1999-4915SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is primarily responsible for coronavirus disease (COVID-19) and it is characterized by respiratory illness with fever and dyspnea. Severe vascular problems and several other manifestations, including neurological ones, have also been frequently reported, particularly in the great majority of “long hauler” patients. SARS-CoV-2 infects and replicates in lung epithelial cells, while dysfunction of endothelial and neuronal brain cells has been observed in the absence of productive infection. It has been shown that the Spike protein can interact with specific cellular receptors, supporting both viral entry and cellular dysfunction. It is thus clear that understanding how and when these receptors are regulated, as well as how much they are expressed would help in unveiling the multifaceted aspects of this disease. Here, we show that SH-SY5Y neuroblastoma cells express three important cellular surface molecules that interact with the Spike protein, namely ACE2, TMPRSS2, and NRP1. Their levels increase when cells are treated with retinoic acid (RA), a commonly used agent known to promote differentiation. This increase matched the higher levels of receptors observed on HUVEC (primary human umbilical vein endothelial cells). We also show by confocal imaging that replication-defective pseudoviruses carrying the SARS-CoV-2 Spike protein can infect differentiated and undifferentiated SH-SY5Y, and HUVEC cells, although with different efficiencies. Neuronal cells and endothelial cells are potential targets for SARS-CoV-2 infection and the interaction of the Spike viral protein with these cells may cause their dysregulation. Characterizing RNA and protein expression tempo, mode, and levels of different SARS-CoV-2 receptors on both cell subpopulations may have clinical relevance for the diagnosis and treatment of COVID-19-infected subjects, including long hauler patients with neurological manifestations.Francesca BenedettiGiovannino SilvestriCarla MavianMatthew WeichseldorferArshi MunawwarMelanie N. CashMelissa DulceyAmy Y. VittorMassimo CiccozziMarco SalemiOlga S. LatinovicDavide ZellaMDPI AGarticleSARS-CoV-2ACE-2SARS-receptorsneuronal cellsendothelial cellsMicrobiologyQR1-502ENViruses, Vol 13, Iss 2193, p 2193 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	SARS-CoV-2 ACE-2 SARS-receptors neuronal cells endothelial cells Microbiology QR1-502
spellingShingle	SARS-CoV-2 ACE-2 SARS-receptors neuronal cells endothelial cells Microbiology QR1-502 Francesca Benedetti Giovannino Silvestri Carla Mavian Matthew Weichseldorfer Arshi Munawwar Melanie N. Cash Melissa Dulcey Amy Y. Vittor Massimo Ciccozzi Marco Salemi Olga S. Latinovic Davide Zella Comparison of SARS-CoV-2 Receptors Expression in Primary Endothelial Cells and Retinoic Acid-Differentiated Human Neuronal Cells
description	SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is primarily responsible for coronavirus disease (COVID-19) and it is characterized by respiratory illness with fever and dyspnea. Severe vascular problems and several other manifestations, including neurological ones, have also been frequently reported, particularly in the great majority of “long hauler” patients. SARS-CoV-2 infects and replicates in lung epithelial cells, while dysfunction of endothelial and neuronal brain cells has been observed in the absence of productive infection. It has been shown that the Spike protein can interact with specific cellular receptors, supporting both viral entry and cellular dysfunction. It is thus clear that understanding how and when these receptors are regulated, as well as how much they are expressed would help in unveiling the multifaceted aspects of this disease. Here, we show that SH-SY5Y neuroblastoma cells express three important cellular surface molecules that interact with the Spike protein, namely ACE2, TMPRSS2, and NRP1. Their levels increase when cells are treated with retinoic acid (RA), a commonly used agent known to promote differentiation. This increase matched the higher levels of receptors observed on HUVEC (primary human umbilical vein endothelial cells). We also show by confocal imaging that replication-defective pseudoviruses carrying the SARS-CoV-2 Spike protein can infect differentiated and undifferentiated SH-SY5Y, and HUVEC cells, although with different efficiencies. Neuronal cells and endothelial cells are potential targets for SARS-CoV-2 infection and the interaction of the Spike viral protein with these cells may cause their dysregulation. Characterizing RNA and protein expression tempo, mode, and levels of different SARS-CoV-2 receptors on both cell subpopulations may have clinical relevance for the diagnosis and treatment of COVID-19-infected subjects, including long hauler patients with neurological manifestations.
format	article
author	Francesca Benedetti Giovannino Silvestri Carla Mavian Matthew Weichseldorfer Arshi Munawwar Melanie N. Cash Melissa Dulcey Amy Y. Vittor Massimo Ciccozzi Marco Salemi Olga S. Latinovic Davide Zella
author_facet	Francesca Benedetti Giovannino Silvestri Carla Mavian Matthew Weichseldorfer Arshi Munawwar Melanie N. Cash Melissa Dulcey Amy Y. Vittor Massimo Ciccozzi Marco Salemi Olga S. Latinovic Davide Zella
author_sort	Francesca Benedetti
title	Comparison of SARS-CoV-2 Receptors Expression in Primary Endothelial Cells and Retinoic Acid-Differentiated Human Neuronal Cells
title_short	Comparison of SARS-CoV-2 Receptors Expression in Primary Endothelial Cells and Retinoic Acid-Differentiated Human Neuronal Cells
title_full	Comparison of SARS-CoV-2 Receptors Expression in Primary Endothelial Cells and Retinoic Acid-Differentiated Human Neuronal Cells
title_fullStr	Comparison of SARS-CoV-2 Receptors Expression in Primary Endothelial Cells and Retinoic Acid-Differentiated Human Neuronal Cells
title_full_unstemmed	Comparison of SARS-CoV-2 Receptors Expression in Primary Endothelial Cells and Retinoic Acid-Differentiated Human Neuronal Cells
title_sort	comparison of sars-cov-2 receptors expression in primary endothelial cells and retinoic acid-differentiated human neuronal cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/78fbba028c134778ab3f1da872855fd0
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Comparison of SARS-CoV-2 Receptors Expression in Primary Endothelial Cells and Retinoic Acid-Differentiated Human Neuronal Cells

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