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Start Over Author "Stacy Gellenoncourt" Topic [sdv.mp.vir]life sciences [q-bio]/microbiology and parasitology/virology
3 results on '"Stacy Gellenoncourt"'

1. SARS-CoV-2 Alpha, Beta, and Delta variants display enhanced Spike-mediated syncytia formation

Author

Mathieu Hubert, Jérémy Dufloo, Rémy Robinot, Hugo Mouquet, Olivier Schwartz, Ludivine Grzelak, Nell Saunders, Elodie Bishop, Françoise Porrot, Delphine Planas, Maaran Michael Rajah, Julian Buchrieser, Lisa A. Chakrabarti, Marija Zivaljic, Alice Bongers, Stacy Gellenoncourt, Florence Guivel-Benhassine, Cyril Planchais, Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Paris Cité (UPCité), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Sorbonne Université (SU), Neurobiologie intégrative des Systèmes cholinergiques / Integrative Neurobiology of Cholinergic Systems (NISC), Institut Pasteur [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Ecole doctorale Cerveau Cognition et Comportement [Paris] (ED 158 - 3C), Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Work in OS lab is funded by Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, ANRS, the Vaccine Research Institute (ANR-10-LABX-77), Fondation Pour la Recherche Médicale (FRM), Labex IBEID (ANR-10-LABX62-IBEID), ANR/FRM Flash Covid PROTEO-SARS-CoV-2, ANR CoronaMito AAP RA-COVID-19 V14, and IDISCOVR. Work in UPBI is funded by grant ANR-10-INSB-04-01 and Région Ile-de-France program DIM1-Health. MMR and MZ are supported by the Pasteur-Paris University (PPU) International Doctoral Program. MMR is also supported by Institut Pasteur Department of Virology 'Bourse de Soudure' fellowship. DP is supported by the Vaccine Research Institute. LG is supported by the French Ministry of Higher Education, Research and Innovation. EB is supported by the Medecine-Sciences ENS-PSL Program. HM laboratory is funded by the Institut Pasteur, the Milieu Intérieur Program (ANR-10-LABX-69- 01), the INSERM, REACTing, EU (RECOVER), and Fondation de France (#00106077) grants., We thank members of the Virus and Immunity Unit for helpful discussions, Dr. Nicoletta Casartelli for her critical reading of the manuscript, and Nathalie Aulner and the UtechS Photonic BioImaging (UPBI) core facility (Institut Pasteur), a member of the France BioImaging network, for image acquisition and analysis support., 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-21-CO14-0007,CoronaMito,Conséquences de l'infection par le SRAS-CoV-2 sur la fonction mitochondriale(2021), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute [Créteil, France] (VRI), Institut Pasteur [Paris] (IP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ziani, Isma, Laboratoires d'excellence - Initiative for the creation of a Vaccine Research Institute - - VRI2010 - ANR-10-LABX-0077 - LABX - VALID, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Protéomique du SARS-CoV-2 - - PROTEO-SARS-CoV-22020 - ANR-20-COVI-0059 - COVID-19 - VALID, Conséquences de l'infection par le SRAS-CoV-2 sur la fonction mitochondriale - - CoronaMito2021 - ANR-21-CO14-0007 - COVID-19 - VALID, Développment d'une infrastructure française distribuée coordonnée - - France-BioImaging2010 - ANR-10-INBS-0004 - INBS - VALID, and Laboratoires d'excellence - GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE - - MILIEU INTERIEUR2010 - ANR-10-LABX-0069 - LABX - VALID

Subjects
fusion, coronavirus, MESH: Spike Glycoprotein, Coronavirus, MESH: Angiotensin-Converting Enzyme 2, medicine.disease_cause, Virus Replication, Giant Cells, SARS‐CoV‐2, MESH: Antibodies, Monoclonal, MESH: Giant Cells, MESH: Chlorocebus aethiops, Chlorocebus aethiops, MESH: Animals, Receptor, Coronavirus, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Syncytium, Strain (chemistry), General Neuroscience, Antibodies, Monoclonal, Articles, Transmembrane protein, Microbiology, Virology & Host Pathogen Interaction, Cell biology, MESH: HEK293 Cells, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Spike Glycoprotein, Coronavirus, MESH: Caco-2 Cells, Angiotensin-Converting Enzyme 2, MESH: Mutation, medicine.drug_class, Immunology, Alpha (ethology), MESH: Vero Cells, Biology, Monoclonal antibody, General Biochemistry, Genetics and Molecular Biology, Article, Cell Line, medicine, Animals, Humans, MESH: SARS-CoV-2, Beta (finance), syncytia, Molecular Biology, Vero Cells, MESH: Humans, General Immunology and Microbiology, SARS-CoV-2, MESH: Virus Replication, spike, MESH: Cell Line, HEK293 Cells, Mutation, Caco-2 Cells
Abstract

Severe COVID‐19 is characterized by lung abnormalities, including the presence of syncytial pneumocytes. Syncytia form when SARS‐CoV‐2 spike protein expressed on the surface of infected cells interacts with the ACE2 receptor on neighboring cells. The syncytia forming potential of spike variant proteins remain poorly characterized. Here, we first assessed Alpha (B.1.1.7) and Beta (B.1.351) spread and fusion in cell cultures, compared with the ancestral D614G strain. Alpha and Beta replicated similarly to D614G strain in Vero, Caco‐2, Calu‐3, and primary airway cells. However, Alpha and Beta formed larger and more numerous syncytia. Variant spike proteins displayed higher ACE2 affinity compared with D614G. Alpha, Beta, and D614G fusion was similarly inhibited by interferon‐induced transmembrane proteins (IFITMs). Individual mutations present in Alpha and Beta spikes modified fusogenicity, binding to ACE2 or recognition by monoclonal antibodies. We further show that Delta spike also triggers faster fusion relative to D614G. Thus, SARS‐CoV‐2 emerging variants display enhanced syncytia formation., Spike protein mutations expressed by emerging SARS‐CoV‐2 variants‐of‐concern differentially affect host cell‐to‐cell fusion, ACE2 receptor binding, and antibody escape.

Published
2021

2. Characterising proteolysis during SARS-CoV-2 infection identifies viral cleavage sites and cellular targets with therapeutic potential

Author

Jeanne Chiaravalli, Marius Walter, Edward Emmott, Emma Sierecki, Stacy Gellenoncourt, Philip Brownridge, Arturas Grauslys, Andrew R. Jones, Fabrice Agou, Charles S. Craik, Marco Vignuzzi, Yann Gambin, Patrick A. Eyers, Lisa A. Chakrabarti, Eric Verdin, Leonard A. Daly, Bjoern Meyer, Dominic P. Bryne, Claire E. Eyers, Populations virales et Pathogenèse - Viral Populations and Pathogenesis, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Criblage chémogénomique et biologique (Plateforme) - Chemogenomic and Biological Screening Platform (PF-CCB), Institut Pasteur [Paris] (IP), Virus et Immunité - Virus and immunity (CNRS-UMR3569), University of Liverpool, Buck Institute for Research on Aging, University of California [San Francisco] (UC San Francisco), University of California (UC), University of New South Wales [Sydney] (UNSW), This work was supported by the Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (grant ANR-10-LABX-62-IBEID) to M.V. S.G. is the recipient of a MESR/Ecole Doctorale BioSPC ED562, Université de Paris fellowship. L.A.C. is supported by Institut Pasteur TASK FORCE SARS COV-2 (Tropicoro project), DIM ELICIT Region Ile-de-France, and ANRS. E.E. is supported by startup funding from the University of Liverpool, as well as a Wellcome Trust ISSF Interdisciplinary & Industry Award. E.E. is grateful for the support of GoFundMe donors for sponsoring SARS-CoV-2 research in his laboratory., and ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010)

Subjects
Proteomics, MESH: Virus Internalization, viruses, medicine.medical_treatment, General Physics and Astronomy, Virus Replication, MESH: Dipeptides, MESH: RNA, Small Interfering, 2.2 Factors relating to the physical environment, MESH: COVID-19, MESH: Animals, MESH: Myosin-Light-Chain Kinase, RNA, Small Interfering, Aetiology, skin and connective tissue diseases, Lung, MESH: Protease Inhibitors, MESH: Viral Proteases, Multidisciplinary, medicine.diagnostic_test, Viral Proteases, MESH: Proteomics, Proteases, Dipeptides, src-Family Kinases, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Infection, Biotechnology, Proto-oncogene tyrosine-protein kinase Src, MESH: Antiviral Agents, MESH: Mutation, Science, Proteolysis, MESH: Proteolysis, Context (language use), Biology, Small Interfering, Antiviral Agents, Article, General Biochemistry, Genetics and Molecular Biology, Cell Line, Vaccine Related, Viral Proteins, Biodefense, medicine, Animals, Humans, Protease Inhibitors, MESH: SARS-CoV-2, Myosin-Light-Chain Kinase, MESH: Humans, Protease, SARS-CoV-2, Prevention, fungi, MESH: Virus Replication, COVID-19, MYLK, Pneumonia, General Chemistry, Virus Internalization, MESH: Viral Proteins, Virology, COVID-19 Drug Treatment, MESH: Cell Line, body regions, Emerging Infectious Diseases, Good Health and Well Being, MESH: src-Family Kinases, Viral replication, Mutation, RNA, Immunization
Abstract

SARS-CoV-2 is the causative agent behind the COVID-19 pandemic, responsible for over 170 million infections, and over 3.7 million deaths worldwide. Efforts to test, treat and vaccinate against this pathogen all benefit from an improved understanding of the basic biology of SARS-CoV-2. Both viral and cellular proteases play a crucial role in SARS-CoV-2 replication. Here, we study proteolytic cleavage of viral and cellular proteins in two cell line models of SARS-CoV-2 replication using mass spectrometry to identify protein neo-N-termini generated through protease activity. We identify previously unknown cleavage sites in multiple viral proteins, including major antigens S and N: the main targets for vaccine and antibody testing efforts. We discover significant increases in cellular cleavage events consistent with cleavage by SARS-CoV-2 main protease, and identify 14 potential high-confidence substrates of the main and papain-like proteases. We show that siRNA depletion of these cellular proteins inhibits SARS-CoV-2 replication, and that drugs targeting two of these proteins: the tyrosine kinase SRC and Ser/Thr kinase MYLK, show a dose-dependent reduction in SARS-CoV-2 titres. Overall, our study provides a powerful resource to understand proteolysis in the context of viral infection, and to inform the development of targeted strategies to inhibit SARS-CoV-2 and treat COVID-19., During SARS-CoV-2 replication, viral and cellular proteases play crucial roles and have been shown to be promising anti-viral targets. Here, Meyer et al. apply mass spectrometry to characterize the proteolytic cleavage profile of viral and cellular proteins in vitro.

Published
2021

3. Low CCR5 expression protects HIV-specific CD4+ T cells of elite controllers from viral entry

Author

Mathieu Claireaux, Rémy Robinot, Jérôme Kervevan, Mandar Patgaonkar, Isabelle Staropoli, Anne Brelot, Alexandre Nouël, Stacy Gellenoncourt, Xian Tang, Mélanie Héry, Stevenn Volant, Emeline Perthame, Véronique Avettand-Fenoël, Julian Buchrieser, Thomas Cokelaer, Christiane Bouchier, Laurence Ma, Faroudy Boufassa, Samia Hendou, Valentina Libri, Milena Hasan, David Zucman, Pierre de Truchis, Olivier Schwartz, Olivier Lambotte, Lisa A. Chakrabarti, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Laboratoire de Microbiologie Clinique [AP-HP Hôpital Necker-Enfants Malades], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biomics (plateforme technologique), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB), Hôpital Foch [Suresnes], Hôpital Raymond Poincaré [AP-HP], Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université Paris-Sud - Paris 11 (UP11), This work was supported by grants to L.A.C. from ANRS (17218 and 19206), Institut Pasteur (PasteurInnov TETRHIS), and ANR (14 CE 16002901). The Biomics Platform is a member of the 'France Génomique' consortium (ANR10-INBS-09-08). M.C. was the recipient of a Sidaction fellowship, R.R. of a Pasteur Carnot MS and a Sidaction fellowships, M.P. of an ANRS fellowship, and S.G. of a MESR/Université de Paris fellowship., We are grateful to patients who participated in the study. We thank the investigators of the ANRS CO21 CODEX cohort and Camille Lecuroux for help with recruitment of controller patients, Morgane Marcou and Katia Bourdic for help with recruitment of treated patients, Bernard Lagane for the gift of plamids, and Sophie Novault from the Pasteur CB UTechS for advice on cell sorting. MHC class II tetramer reagents were provided by the NIH Tetramer Core facility at Emory University. The following reagent was obtained through the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH: HIV-1 PTE Gag peptide set (Cat # 11554)., ANR-14-CE16-0029,PD1VAX,Une nouvelle stratégie de vaccination par vecteur ADN PD1 pour mimer les réponses spécifiques de Gag trouvées chez les contrôleurs spontanés du VIH(2014), and ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010)

Subjects
CD4-Positive T-Lymphocytes, Viral membrane fusion, MESH: Mutation, Receptors, CXCR3, Receptors, CCR5, Science, MESH: Virus Internalization, viruses, General Physics and Astronomy, Down-Regulation, Gene Products, gag, HIV Infections, MESH: Receptors, CCR5, MESH: Down-Regulation, General Biochemistry, Genetics and Molecular Biology, Article, MESH: Receptors, CXCR3, MESH: HIV-1, MESH: Elite Controllers, Humans, MESH: Humans, Multidisciplinary, Retrovirus, Histocompatibility Antigens Class II, MESH: CD4-Positive T-Lymphocytes, virus diseases, MESH: HIV Infections, General Chemistry, Virus Internalization, MESH: Chemokines, MESH: Gene Expression Regulation, Gene Expression Regulation, MESH: Gene Products, gag, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Mutation, MESH: Histocompatibility Antigens Class II, HIV-1, Chemokines, Elite Controllers
Abstract

HIV elite controllers maintain a population of CD4 + T cells endowed with high avidity for Gag antigens and potent effector functions. How these HIV-specific cells avoid infection and depletion upon encounter with the virus remains incompletely understood. Ex vivo characterization of single Gag-specific CD4 + T cells reveals an advanced Th1 differentiation pattern in controllers, except for the CCR5 marker, which is downregulated compared to specific cells of treated patients. Accordingly, controller specific CD4 + T cells show decreased susceptibility to CCR5-dependent HIV entry. Two controllers carried biallelic mutations impairing CCR5 surface expression, indicating that in rare cases CCR5 downregulation can have a direct genetic cause. Increased expression of β-chemokine ligands upon high-avidity antigen/TCR interactions contributes to autocrine CCR5 downregulation in controllers without CCR5 mutations. These findings suggest that genetic and functional regulation of the primary HIV coreceptor CCR5 play a key role in promoting natural HIV control., Here, Claireaux et al. show that people who naturally control HIV infection express lower levels of the viral co-receptor CCR5 in specific CD4+ T cells, and that this results from mutations or receptor internalization by CD4+ T cell-produced chemokines.

Published
2019

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