| Title: |
TMPRSS2 is a functional receptor for human coronavirus HKU1 |
| Authors: |
Saunders, Nell; Fernandez, Ignacio; Planchais, Cyril; Michel, Vincent; Rajah, Maaran Michael; Baquero Salazar, Eduard; Postal, Jeanne; Porrot, Francoise; Guivel-Benhassine, Florence; Blanc, Catherine; Chauveau-Le Friec, Gaëlle; Martin, Augustin; Grzelak, Ludivine; Oktavia, Rischa Maya; Meola, Annalisa; Ahouzi, Olivia; Hoover-Watson, Hunter; Prot, Matthieu; Delaune, Deborah; Cornelissen, Marion; Deijs, Martin; Meriaux, Véronique; Mouquet, Hugo; Simon-Lorière, Etienne; van der Hoek, Lia; Lafaye, Pierre; Rey, Felix; Buchrieser, Julian; Schwartz, Olivier |
| Contributors: |
Virus et Immunité - Virus and immunity (CNRS-UMR3569); Institut Pasteur Paris (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité); Virologie Structurale - Structural Virology; Immunologie humorale - Humoral Immunology; Institut Pasteur Paris (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité); Pathogénèse des Infections vasculaires / Pathogenesis of Vascular Infections; Plateforme technologique Nanoimagerie / Nanoimaging Technological Platform; Institut Pasteur Paris (IP)-Université Paris Cité (UPCité); Laboratoire commun Pasteur-TheraVectys; Institut Pasteur Paris (IP)-TheraVectys-Université Paris Cité (UPCité); Ingénierie des Anticorps (plate-forme) - Antibody Engineering (Platform); Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses; Institut de Recherche Biomédicale des Armées Brétigny-sur-Orge (IRBA); Universiteit van Amsterdam = University of Amsterdam (UvA); Amsterdam University Medical Centers (Amsterdam UMC); Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae Paris (CNR - laboratoire coordonnateur); Institut Pasteur Paris (IP); Vaccine Research Institute Créteil, France (VRI); Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12); N.S. is funded by the Ministère de l’Enseignement supérieur et de la Recherche. O.S.’s laboratory is funded by Institut Pasteur, Fondation pour la Recherche Médicale, the National Agency for AIDS Research–Emerging Infectious Diseases, the Vaccine Research Institute (ANR-10-LABX-77), Humanities in the European Research Area programme (DURABLE consortium), Labex Integrative Biology of Emerging Infectious Diseases (IBEID) (ANR-10-LABX-62-IBEID), Agence Nationale de la Recherche (ANR)/Fondation pour la Recherche Médicale Flash Covid PROTEO-SARS-CoV-2 and IDISCOVR. E.S.-L.’s lab is funded by the INCEPTION programme (Investissements d’Avenir grant no. ANR-16-CONV-0005), the National Institutes of Health Pasteur International Center for Research on Emerging Infectious Diseases programme (award no. U01AI151758), the Health Emergency Preparedness and Response European programme DURABLE (101102733) and the Labex IBEID (ANR-10-LABX-62-IBEID). H.M.’s laboratory is funded by the Institut Pasteur, the Milieu Intérieur Programme (ANR-10-LABX-69-01) and L'Institut national de la santé et de la recherche médicale, REACTing and European Union (Rapid European COVID-19 Emergency Response (RECOVER)) grants. M.M.R. was supported by the Pasteur-Paris University International Doctoral Programme and the Institut Pasteur Department of Virology ‘Bourse de Soudure’ fellowship. F.R.’s laboratory is funded by ANR grant nos. ANR-13-ISV8-0002-01 and ANR-10-LABX-62-10 IBEID, Wellcome Trust collaborative grant no. UNS22082 and the Institut Pasteur and the Centre national de la recherche scientifique. Work with UtechS Photonic BioImaging is funded by grant no. ANR-10-INSB-04-01 and Région Ile-de-France programme DIM1-Health.; ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010); ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010); ANR-20-COVI-0059,PROTEO-SARS-CoV-2,Protéomique du SARS-CoV-2(2020); ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016); ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010); ANR-13-ISV8-0002,flavistem,La protéine E des flavivirus : interactions et fusion membranaire(2013); ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010) |
| Source: |
ISSN: 0028-0836. |
| Publisher Information: |
CCSD; Nature Publishing Group |
| Publication Year: |
2023 |
| Subject Terms: |
[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology; [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases; [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases |
| Description: |
International audience ; Four endemic seasonal human coronaviruses causing common colds circulate worldwide: HKU1, 229E, NL63 and OC43 (ref. 1). After binding to cellular receptors, coronavirus spike proteins are primed for fusion by transmembrane serine protease 2 (TMPRSS2) or endosomal cathepsins2,3,4,5,6,7,8,9. NL63 uses angiotensin-converting enzyme 2 as a receptor10, whereas 229E uses human aminopeptidase-N11. HKU1 and OC43 spikes bind cells through 9-O-acetylated sialic acid, but their protein receptors remain unknown12. Here we show that TMPRSS2 is a functional receptor for HKU1. TMPRSS2 triggers HKU1 spike-mediated cell–cell fusion and pseudovirus infection. Catalytically inactive TMPRSS2 mutants do not cleave HKU1 spike but allow pseudovirus infection. Furthermore, TMPRSS2 binds with high affinity to the HKU1 receptor binding domain (Kd 334 and 137 nM for HKU1A and HKU1B genotypes) but not to SARS-CoV-2. Conserved amino acids in the HKU1 receptor binding domain are essential for binding to TMPRSS2 and pseudovirus infection. Newly designed anti-TMPRSS2 nanobodies potently inhibit HKU1 spike attachment to TMPRSS2, fusion and pseudovirus infection. The nanobodies also reduce infection of primary human bronchial cells by an authentic HKU1 virus. Our findings illustrate the various evolution strategies of coronaviruses, which use TMPRSS2 to either directly bind to target cells or prime their spike for membrane fusion and entry. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/37879362; PUBMED: 37879362 |
| DOI: |
10.1038/s41586-023-06761-7 |
| Availability: |
https://hal.science/hal-04372694; https://hal.science/hal-04372694v1/document; https://hal.science/hal-04372694v1/file/ilovepdf_merged_merged.pdf; https://doi.org/10.1038/s41586-023-06761-7 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.52137F0F |
| Database: |
BASE |