Differential Effect of SARS-CoV-2 Spike Glycoprotein 1 on Human Bronchial and Alveolar Lung Mucosa Models: Implications for Pathogenicity.

Angiotensin-Converting Enzyme 2 / metabolism Bronchi / metabolism Cytokines / metabolism Gene Expression Profiling Humans Lung / metabolism Models, Biological Protein Interaction Domains and Motifs Recombinant Proteins / chemistry Respiratory Mucosa / metabolism SARS-CoV-2 / metabolism Spike Glycoprotein, Coronavirus / chemistry Toll-Like Receptor 2 / metabolism Toll-Like Receptor 4 / metabolism
COVID-19 MERS (middle east respiratory syndrome) SARS (severe acute respiratory syndrome) SARS-CoV-2 coronavirus fibrosis lung pulmonary spike protein

Journal

Viruses
ISSN: 1999-4915
Titre abrégé: Viruses
Pays: Switzerland
ID NLM: 101509722

Informations de publication

Date de publication:
17 12 2021
Historique:
received: 12 10 2021
revised: 10 12 2021
accepted: 11 12 2021
entrez: 28 12 2021
pubmed: 29 12 2021
medline: 7 1 2022
Statut: epublish

Résumé

The SARS-CoV-2 spike protein mediates attachment of the virus to the host cell receptor and fusion between the virus and the cell membrane. The S1 subunit of the spike glycoprotein (S1 protein) contains the angiotensin converting enzyme 2 (ACE2) receptor binding domain. The SARS-CoV-2 variants of concern contain mutations in the S1 subunit. The spike protein is the primary target of neutralizing antibodies generated following infection, and constitutes the viral component of mRNA-based COVID-19 vaccines. Therefore, in this work we assessed the effect of exposure (24 h) to 10 nM SARS-CoV-2 recombinant S1 protein on physiologically relevant human bronchial (bro) and alveolar (alv) lung mucosa models cultured at air-liquid interface (ALI) ( Exposure to S1 protein induced the surface expression of ACE2, toll like receptor (TLR) 2, and TLR4 in both bro-ALI and alv-ALI models. Transcript expression analysis identified 117 (bro-ALI) and 97 (alv-ALI) differentially regulated genes ( In conclusion, we observed a typical anti-viral response in the bronchial model and a pro-fibrotic response in the alveolar model. The bro-ALI and alv-ALI models may serve as an easy and robust platform for assessing the pathogenicity of SARS-CoV-2 variants of concern at different lung regions.

Sections du résumé

BACKGROUND
The SARS-CoV-2 spike protein mediates attachment of the virus to the host cell receptor and fusion between the virus and the cell membrane. The S1 subunit of the spike glycoprotein (S1 protein) contains the angiotensin converting enzyme 2 (ACE2) receptor binding domain. The SARS-CoV-2 variants of concern contain mutations in the S1 subunit. The spike protein is the primary target of neutralizing antibodies generated following infection, and constitutes the viral component of mRNA-based COVID-19 vaccines.
METHODS
Therefore, in this work we assessed the effect of exposure (24 h) to 10 nM SARS-CoV-2 recombinant S1 protein on physiologically relevant human bronchial (bro) and alveolar (alv) lung mucosa models cultured at air-liquid interface (ALI) (
RESULTS
Exposure to S1 protein induced the surface expression of ACE2, toll like receptor (TLR) 2, and TLR4 in both bro-ALI and alv-ALI models. Transcript expression analysis identified 117 (bro-ALI) and 97 (alv-ALI) differentially regulated genes (
CONCLUSIONS
In conclusion, we observed a typical anti-viral response in the bronchial model and a pro-fibrotic response in the alveolar model. The bro-ALI and alv-ALI models may serve as an easy and robust platform for assessing the pathogenicity of SARS-CoV-2 variants of concern at different lung regions.

Identifiants

DOI: 10.3390/v13122537 PMID: 34960806 PMC: PMC8708014
pubmed: 34960806
pii: v13122537
doi: 10.3390/v13122537
pmc: PMC8708014
pii:
doi:

Substances chimiques

Cytokines 0
Recombinant Proteins 0
Spike Glycoprotein, Coronavirus 0
TLR2 protein, human 0
TLR4 protein, human 0
Toll-Like Receptor 2 0
Toll-Like Receptor 4 0
spike protein, SARS-CoV-2 0
ACE2 protein, human EC 3.4.17.23
Angiotensin-Converting Enzyme 2 EC 3.4.17.23

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Swedish Research Council
ID : LP: 2018-03233
Organisme : IMM strategic grant
ID : SU-COVID (2020-2021)
Organisme : Swedish Heart Lung Foundation
ID : (KG: 20200776)

Références

EMBO Mol Med. 2012 Sep;4(9):939-51
pubmed: 22684844
Eur Respir J Suppl. 2001 Dec;34:3s-17s
pubmed: 12392030
Front Immunol. 2020 Sep 29;11:585647
pubmed: 33133104
Diabetes. 2020 Dec;69(12):2691-2699
pubmed: 33024003
J Clin Med. 2021 Sep 02;10(17):
pubmed: 34501430
Eur Respir J. 2020 Oct 8;56(4):
pubmed: 32764117
Virchows Arch. 2010 Nov;457(5):563-75
pubmed: 20857141
Nat Immunol. 2021 Jul;22(7):829-838
pubmed: 33963333
Toxicol Sci. 2018 Jul 1;164(1):21-30
pubmed: 29534242
Nat Immunol. 2021 Jul;22(7):801-802
pubmed: 34103714
J Cell Biochem. 2018 Nov 2;:
pubmed: 30390331
Sci Rep. 2020 Nov 24;10(1):20460
pubmed: 33235237
Int Arch Allergy Immunol. 2003 Oct;132(2):168-76
pubmed: 14600429
Nat Rev Microbiol. 2021 Jul;19(7):409-424
pubmed: 34075212
Int J Biochem Cell Biol. 2008;40(10):2174-82
pubmed: 18395486
PLoS One. 2017 Jan 20;12(1):e0170428
pubmed: 28107509
J Med Virol. 2021 May;93(5):2735-2739
pubmed: 33506952
FEBS Lett. 1992 May 18;302(3):231-4
pubmed: 1601130
Nanotoxicology. 2019 Dec;13(10):1362-1379
pubmed: 31462114
N Engl J Med. 2020 Jul 9;383(2):120-128
pubmed: 32437596
J Cell Physiol. 1996 May;167(2):290-6
pubmed: 8613470
Toxicol In Vitro. 2019 Dec;61:104617
pubmed: 31381966
Nat Commun. 2020 Oct 28;11(1):5453
pubmed: 33116139
Hum Gene Ther. 2018 Nov;29(11):1242-1251
pubmed: 29598007
Cell Death Discov. 2021 Mar 15;7(1):52
pubmed: 33723241
Vascul Pharmacol. 2021 Apr;137:106823
pubmed: 33232769
Mediators Inflamm. 2021 Jan 14;2021:8874339
pubmed: 33505220
Am J Physiol Lung Cell Mol Physiol. 2011 Mar;300(3):L341-53
pubmed: 21131395
Int Immunopharmacol. 2021 Nov;100:108145
pubmed: 34547678
Nucleic Acids Res. 2019 Jul 2;47(W1):W191-W198
pubmed: 31066453
J Rheumatol. 2007 Oct;34(10):2056-62
pubmed: 17896803
Biochim Biophys Acta Biomembr. 2020 May 1;1862(5):183205
pubmed: 32001212
Elife. 2020 Nov 09;9:
pubmed: 33164751
Virus Res. 2009 Jun;142(1-2):19-27
pubmed: 19185596
Vaccines (Basel). 2021 Jan 11;9(1):
pubmed: 33440640
Mol Aspects Med. 2019 Feb;65:56-69
pubmed: 30130563
Chest. 1993 Jul;104(1):47-53
pubmed: 8325116
J Med Virol. 2021 Jan;93(1):250-256
pubmed: 32592501
J Immunol. 1993 May 1;150(9):4188-96
pubmed: 8473757
Am J Physiol Lung Cell Mol Physiol. 2001 Jul;281(1):L92-7
pubmed: 11404251
Am J Physiol Lung Cell Mol Physiol. 2018 Jan 1;314(1):L127-L136
pubmed: 28860143
Elife. 2021 Dec 06;10:
pubmed: 34866574
Semin Immunopathol. 2016 Jul;38(4):517-34
pubmed: 27001429
Arch Virol. 2021 Mar;166(3):675-696
pubmed: 33462671
Intern Emerg Med. 2020 Oct;15(7):1333-1334
pubmed: 32415560
Am J Pathol. 2003 Jul;163(1):345-54
pubmed: 12819039
J Clin Invest. 2007 Dec;117(12):3786-99
pubmed: 17992263
Immunol Rev. 2021 Jul;302(1):228-240
pubmed: 34028807
Am J Respir Cell Mol Biol. 2003 Oct;29(4):490-8
pubmed: 12714376
Nat Biotechnol. 2020 Aug;38(8):970-979
pubmed: 32591762

Auteurs

Mizanur Rahman (M)

Unit of Integrative Toxicology, Institute of Environmental Medicine, Karolinska Institutet, 17 177 Stockholm, Sweden.

Martin Irmler (M)

Institute of Experimental Genetics, Helmholtz Zentrum München GmbH, 85764 Neuherberg, Germany.

Sandeep Keshavan (S)

Adolphe Merkle Institute, University of Fribourg, Chemin des Verdiers 4, 1700 Fribourg, Switzerland.
ORCID: 0000-0002-2403-4083

Micol Introna (M)

Unit of Integrative Toxicology, Institute of Environmental Medicine, Karolinska Institutet, 17 177 Stockholm, Sweden.
ORCID: 0000-0002-5564-1994

Johannes Beckers (J)

Institute of Experimental Genetics, Helmholtz Zentrum München GmbH, 85764 Neuherberg, Germany.
German Center for Diabetes Research (DZD e.V.), 85764 Neuherberg, Germany.
Chair of Experimental Genetics, Technical University of Munich, 85354 Freising, Germany.
ORCID: 0000-0002-1038-7160

Lena Palmberg (L)

Unit of Integrative Toxicology, Institute of Environmental Medicine, Karolinska Institutet, 17 177 Stockholm, Sweden.

Gunnar Johanson (G)

Unit of Integrative Toxicology, Institute of Environmental Medicine, Karolinska Institutet, 17 177 Stockholm, Sweden.
ORCID: 0000-0002-8759-9567

Koustav Ganguly (K)

Unit of Integrative Toxicology, Institute of Environmental Medicine, Karolinska Institutet, 17 177 Stockholm, Sweden.
ORCID: 0000-0001-8531-8154

Swapna Upadhyay (S)

Unit of Integrative Toxicology, Institute of Environmental Medicine, Karolinska Institutet, 17 177 Stockholm, Sweden.

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Classifications MeSH

questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Peptide hydrolases › Exopeptidases › Carboxypeptidases › Angiotensin-converting enzyme 2 › Differential Effect of SARS-CoV-2 Spike...
questionsmedicales.fr › Appareil respiratoire › Poumon › Bronches › Differential Effect of SARS-CoV-2 Spike...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Differential Effect of SARS-CoV-2 Spike...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de profil d'expression de gènes › Differential Effect of SARS-CoV-2 Spike...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Differential Effect of SARS-CoV-2 Spike...
questionsmedicales.fr › Appareil respiratoire › Poumon › Differential Effect of SARS-CoV-2 Spike...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Differential Effect of SARS-CoV-2 Spike...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Conformation moléculaire › Conformation des protéines › Éléments structuraux des protéines › Motifs et domaines d'intéraction protéique › Differential Effect of SARS-CoV-2 Spike...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines recombinantes › Differential Effect of SARS-CoV-2 Spike...
questionsmedicales.fr › Tissus › Membranes › Muqueuse › Muqueuse respiratoire › Differential Effect of SARS-CoV-2 Spike...
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN à brin positif › Nidovirales › Coronaviridae › Coronavirus › Betacoronavirus › Virus du SRAS › SARS-CoV-2 › Differential Effect of SARS-CoV-2 Spike...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines virales › Protéines virales structurales › Protéines de l'enveloppe virale › Protéines de fusion virale › Glycoprotéine de spicule des coronavirus › Differential Effect of SARS-CoV-2 Spike...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Récepteurs de reconnaissance de motifs moléculaires › Récepteurs de type Toll › Récepteur de type Toll-2 › Differential Effect of SARS-CoV-2 Spike...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Récepteurs de reconnaissance de motifs moléculaires › Récepteurs de type Toll › Récepteur de type Toll-4 › Differential Effect of SARS-CoV-2 Spike...