Evidence map›Paper›PMID 34325716›Full record

ArticleJournal of neuroinflammation2021

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

Silvia Torices, Rosalba Cabrera, Michael Stangis, Oandy Naranjo, Nikolai Fattakhov, Timea Teglas, Daniel Adesse, Michal Toborek

Open access · goldAbstract read
In one paragraph

Article in Journal of neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
5.9field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

42 citing papers in PubMed, 65 citations in OpenAlex.

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  9. Interactions of SARS-CoV-2 with Human Target Cells-A Metabolic View.International journal of molecular sciences · 2024
    Review
  10. Article
  11. Article
  12. Article
  13. Occludin: a gatekeeper of brain Infection by HIV-1.Fluids and barriers of the CNS · 2023
    Review
  14. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 2 countries.

Silvia ToricesDepartment of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, 528E Gautier Bldg. 1011 NW 15th Street, Miami, FL, 33136, USA. sxt736@med.miami.edu.
Rosalba CabreraDepartment of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, 528E Gautier Bldg. 1011 NW 15th Street, Miami, FL, 33136, USA.
Michael StangisDepartment of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, 528E Gautier Bldg. 1011 NW 15th Street, Miami, FL, 33136, USA.
Oandy NaranjoDepartment of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, 528E Gautier Bldg. 1011 NW 15th Street, Miami, FL, 33136, USA.
Nikolai FattakhovDepartment of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, 528E Gautier Bldg. 1011 NW 15th Street, Miami, FL, 33136, USA.
Timea TeglasDepartment of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, 528E Gautier Bldg. 1011 NW 15th Street, Miami, FL, 33136, USA.
Daniel AdesseLaboratory of Structural Biology, Instituto Oswaldo Cruz, Fiocruz, CEP, Rio de Janeiro, RJ, 21045-900, Brazil.
Michal ToborekDepartment of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, 528E Gautier Bldg. 1011 NW 15th Street, Miami, FL, 33136, USA. mtoborek@med.miami.edu.ORCID http://orcid.org/0000-0003-4475-2119
University of Miami · USFundação Oswaldo Cruz · BR

Funding

Tat, amyloid beta and brain endothelial barrier functionR01MH072567 · NIMH · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI Michal Toborek · 2005 to 2026
$7.6M
Role of cerebral vasculature in brain ischemia in HIV infectionR01HL126559 · NHLBI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI TOBOREK, MICHAL · 2014 to 2024
$3.8M
To evaluate the role of cannabinoid signaling during the comorbidity of HIV and Alzheimer¿s disease in the context of HIV-associated cognitive disordersR01DA040537 · NIDA · FLORIDA INTERNATIONAL UNIVERSITY · PI NAIR, MADHAVAN P. · 2015 to 2019
$3.0M
Targeting Inflammasomes in Substance Abuse and HIVR01DA050528 · NIDA · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI TOBOREK, MICHAL · 2020 to 2024
$2.3M
Defining brain pericytes as a novel and myeloid-derived HIV reservoirR01MH128022 · NIMH · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI TOBOREK, MICHAL · 2021 to 2025
$2.3M
Prevention of HIV and drug abuse-induced brain pathology by targeting mitochondriaR01DA044579 · NIDA · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI TOBOREK, MICHAL · 2017 to 2021
$2.2M
Role of the BBB in HIV brain infection during methamphetamine abuseR01DA039576 · NIDA · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI TOBOREK, MICHAL · 2015 to 2019
$2.0M
Interplay between cArt, HIV, and amyloid at the blood-brain barrier.R01MH098891 · NIMH · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI TOBOREK, MICHAL · 2012 to 2016
$1.9M
Novel role of inflammasome activation in ART neurotoxicityR21MH122235 · NIMH · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI TOBOREK, MICHAL · 2020 to 2021
$422k
American Heart Association 20POST35211181Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro SEI-260003/002704/2020Fundação Oswaldo Cruz 48401984391807NHLBI NIH HHS HL126559NHLBI NIH HHS R01 HL126559NIDA NIH HHS DA039576, DA040537, and DA044579NIDA NIH HHS R01 DA039576NIDA NIH HHS R01 DA040537NIDA NIH HHS R01 DA044579NIDA NIH HHS R01 DA050528NIMH NIH HHS MH098891, MH07256NIMH NIH HHS R01 MH072567NIMH NIH HHS R01 MH098891NIMH NIH HHS R01 MH128022NIMH NIH HHS R21 MH122235
6 · The paper itself

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.

Indexed as

HIV-1SARS-CoV-2Angiotensin-Converting Enzyme 2AstrocytesBlood VesselsBrain DiseasesCells, CulturedCOVID-19Endothelium, VascularHIV InfectionsHumansMicrogliaNervous System DiseasesNeuronsPrimary Cell CultureReceptor, Angiotensin, Type 2ACE2 protein, humanAngiotensin-Converting Enzyme 2Receptor, Angiotensin, Type 2Receptors, VirusACE2Blood-brain barrierHIV-1SARS-CoV-2TMPRSS2

Identifiers

PMID34325716
PMCPMC8319595
OpenAlexW3129370010

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.