1. Extracellular vesicles containing ACE2 efficiently prevent infection by SARS‐CoV‐2 Spike protein‐containing virus
- Author
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Nicolas Manel, Clotilde Théry, Olivier Schwartz, Federico Cocozza, Nathalie Névo, Mercedes Tkach, Julian Buchrieser, Xavier Lahaye, Lorena Martin-Jaular, Ester Piovesana, Immunité et cancer (U932), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie [Paris], Université Paris sciences et lettres (PSL), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université de Paris (UP), This work was supported by Institut Curie, INSERM, CNRS, grants H2020-MSCA-ITN (722148, TRAIN-EV), INCa (11548) and Fondation ARC (PGA1 RF20180206962) to C Théry, LABEX DCBIOL (ANR-10-IDEX-0001-02 PSL* and ANR-11-LABX-0043) to C. Théry and N. Manel, LABEX VRI (ANR-10-LABX-77), ANRS (France Recherche Nord & Sud Sida-HIV Hépatites, ECTZ36691, ECTZ71745), Sidaction (17-1-AAE-11097-2), ANR (ANR-19-CE15-0018-01, ANR-18-CE92-0022-01), DIM1HEALTH to N Manel. N Manel thanks Mutuelle Bleue for support., ANR-10-IDEX-0001,PSL,Paris Sciences et Lettres(2010), ANR-11-LABX-0043,DCBIOL,Biologie des cellules dendritiques(2011), ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-19-CE15-0018,NUCLEONDRIA,Fonctions émergentes du détection de l'immunité innée cGAS dans les organites à ADN(2019), ANR-18-CE92-0022,cGAS-Vac,Analyses fonctionnelles de la voie cGAS/STING au cours d'infections bactériennes et infections virales et implications pour le développement de vaccins innovants(2018), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), LAHAYE, Xavier, Initiative d'excellence - Paris Sciences et Lettres - - PSL2010 - ANR-10-IDEX-0001 - IDEX - VALID, Biologie des cellules dendritiques - - DCBIOL2011 - ANR-11-LABX-0043 - LABX - VALID, Laboratoires d'excellence - Initiative for the creation of a Vaccine Research Institute - - VRI2010 - ANR-10-LABX-0077 - LABX - VALID, Fonctions émergentes du détection de l'immunité innée cGAS dans les organites à ADN - - NUCLEONDRIA2019 - ANR-19-CE15-0018 - AAPG2019 - VALID, APPEL À PROJETS GÉNÉRIQUE 2018 - Analyses fonctionnelles de la voie cGAS/STING au cours d'infections bactériennes et infections virales et implications pour le développement de vaccins innovants - - cGAS-Vac2018 - ANR-18-CE92-0022 - AAPG2018 - VALID, and Virus et Immunité - Virus and immunity (CNRS-UMR3569)
- Subjects
0301 basic medicine ,Histology ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,Short Communication ,viruses ,Priming (immunology) ,ACE2 ,urologic and male genital diseases ,TMPRSS2 ,Virus ,SARS‐CoV‐2 ,Cell Line ,03 medical and health sciences ,Extracellular Vesicles ,0302 clinical medicine ,Humans ,Receptor ,skin and connective tissue diseases ,Infectivity ,Innate immune system ,biology ,Chemistry ,SARS-CoV-2 ,Lentivirus ,Serine Endopeptidases ,Lipid bilayer fusion ,COVID-19 ,Cell Biology ,Virus Internalization ,biology.organism_classification ,Cell biology ,030104 developmental biology ,030220 oncology & carcinogenesis ,Spike Glycoprotein, Coronavirus ,Receptors, Virus ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Angiotensin-Converting Enzyme 2 ,EV therapy ,Caco-2 Cells ,hormones, hormone substitutes, and hormone antagonists - Abstract
International audience; SARS-CoV-2 entry is mediated by binding of the spike protein (S) to the surface receptor ACE2 and subsequent priming by host TMPRSS2 allowing membrane fusion. Here, we produced extracellular vesicles (EVs) exposing ACE2 and demonstrate that ACE2-EVs are efficient decoys for SARS-CoV-2 S protein-containing lentivirus. Reduction of infectivity positively correlates with the level of ACE2, is much more efficient than with soluble ACE2 and further enhanced by the inclusion of TMPRSS2.
- Published
- 2020