17 results on '"Elodie Décembre"'
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2. Adaptation to host cell environment during experimental evolution of Zika virus
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Vincent Grass, Emilie Hardy, Kassian Kobert, Soheil Rastgou Talemi, Elodie Décembre, Coralie Guy, Peter V. Markov, Alain Kohl, Mathilde Paris, Anja Böckmann, Sara Muñoz-González, Lee Sherry, Thomas Höfer, Bastien Boussau, and Marlène Dreux
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Biology (General) ,QH301-705.5 - Abstract
In vitro analyses and computational modelling indicate that Zika virus adapts to the cellular environment of its host over time
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- 2022
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3. Sensing of cell-associated HTLV by plasmacytoid dendritic cells is regulated by dense β-galactoside glycosylation.
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Sonia Assil, Nicolas Futsch, Elodie Décembre, Sandrine Alais, Antoine Gessain, François-Loïc Cosset, Renaud Mahieux, Marlène Dreux, and Hélène Dutartre
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Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
Human T Lymphotropic virus (HTLV) infection can persist in individuals resulting, at least in part, from viral escape of the innate immunity, including inhibition of type I interferon response in infected T-cells. Plasmacytoid dendritic cells (pDCs) are known to bypass viral escape by their robust type I interferon production. Here, we demonstrated that pDCs produce type I interferons upon physical cell contact with HTLV-infected cells, yet pDC activation inversely correlates with the ability of the HTLV-producing cells to transmit infection. We show that pDCs sense surface associated-HTLV present with glycan-rich structure referred to as biofilm-like structure, which thus represents a newly described viral structure triggering the antiviral response by pDCs. Consistently, heparan sulfate proteoglycans and especially the cell surface pattern of terminal β-galactoside glycosylation, modulate the transmission of the immunostimulatory RNA to pDCs. Altogether, our results uncover a function of virus-containing cell surface-associated glycosylated structures in the activation of innate immunity.
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- 2019
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4. Plasmacytoid dendritic cells control dengue and Chikungunya virus infections via IRF7-regulated interferon responses
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Brian Webster, Scott W Werneke, Biljana Zafirova, Sébastien This, Séverin Coléon, Elodie Décembre, Helena Paidassi, Isabelle Bouvier, Pierre-Emmanuel Joubert, Darragh Duffy, Thierry Walzer, Matthew L Albert, and Marlène Dreux
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mouse ,immunology ,virology ,dendritic cells ,interferons ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
Type I interferon (IFN-I) responses are critical for the control of RNA virus infections, however, many viruses, including Dengue (DENV) and Chikungunya (CHIKV) virus, do not directly activate plasmacytoid dendritic cells (pDCs), robust IFN-I producing cells. Herein, we demonstrated that DENV and CHIKV infected cells are sensed by pDCs, indirectly, resulting in selective IRF7 activation and IFN-I production, in the absence of other inflammatory cytokine responses. To elucidate pDC immunomodulatory functions, we developed a mouse model in which IRF7 signaling is restricted to pDC. Despite undetectable levels of IFN-I protein, pDC-restricted IRF7 signaling controlled both viruses and was sufficient to protect mice from lethal CHIKV infection. Early pDC IRF7-signaling resulted in amplification of downstream antiviral responses, including an accelerated natural killer (NK) cell-mediated type II IFN response. These studies revealed the dominant, yet indirect role of pDC IRF7-signaling in directing both type I and II IFN responses during arbovirus infections.
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- 2018
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5. Sensing of immature particles produced by dengue virus infected cells induces an antiviral response by plasmacytoid dendritic cells.
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Elodie Décembre, Sonia Assil, Marine L B Hillaire, Wanwisa Dejnirattisai, Juthathip Mongkolsapaya, Gavin R Screaton, Andrew D Davidson, and Marlène Dreux
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Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
Dengue virus (DENV) is the leading cause of mosquito-borne viral illness and death in humans. Like many viruses, DENV has evolved potent mechanisms that abolish the antiviral response within infected cells. Nevertheless, several in vivo studies have demonstrated a key role of the innate immune response in controlling DENV infection and disease progression. Here, we report that sensing of DENV infected cells by plasmacytoid dendritic cells (pDCs) triggers a robust TLR7-dependent production of IFNα, concomitant with additional antiviral responses, including inflammatory cytokine secretion and pDC maturation. We demonstrate that unlike the efficient cell-free transmission of viral infectivity, pDC activation depends on cell-to-cell contact, a feature observed for various cell types and primary cells infected by DENV, as well as West Nile virus, another member of the Flavivirus genus. We show that the sensing of DENV infected cells by pDCs requires viral envelope protein-dependent secretion and transmission of viral RNA. Consistently with the cell-to-cell sensing-dependent pDC activation, we found that DENV structural components are clustered at the interface between pDCs and infected cells. The actin cytoskeleton is pivotal for both this clustering at the contacts and pDC activation, suggesting that this structural network likely contributes to the transmission of viral components to the pDCs. Due to an evolutionarily conserved suboptimal cleavage of the precursor membrane protein (prM), DENV infected cells release uncleaved prM containing-immature particles, which are deficient for membrane fusion function. We demonstrate that cells releasing immature particles trigger pDC IFN response more potently than cells producing fusion-competent mature virus. Altogether, our results imply that immature particles, as a carrier to endolysosome-localized TLR7 sensor, may contribute to regulate the progression of dengue disease by eliciting a strong innate response.
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- 2014
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6. Tracking Plasmacytoid Dendritic Cell Response to Physical Contact with Infected Cells
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Margarida Sá Ribeiro, Garima Joshi, Elodie Décembre, Célia Nuovo, Adrien Bosseboeuf, Alicia Bellomo, Manon Venet, Sonia Assil, and Marlène Dreux
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- 2023
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7. Adaptation to host cell environment during experimental evolution of Zika virus
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Sara Munoz-Gonzalez, Coralie Guy, Elodie Décembre, Peter Markov, Bastien Boussau, Alain Kohl, Marlène Dreux, Mathilde Paris, Thomas Höfer, Kassian Kobert, Vincent Grass, Soheil Rastgou Talemi, Emilie Hardy, Anja Böckmann, Lee Sherry, Trafic Vésiculaire, Réponse Innée et Virus – Vesicular trafficking, Innate response, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Luxembourg Institute of Health (LIH), MRC - University of Glasgow Centre for Virus Research, Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), Institut de Génomique Fonctionnelle de Lyon (IGFL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Microbiologie moléculaire et biochimie structurale / Molecular Microbiology and Structural Biochemistry (MMSB), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Le Cocon, Département PEGASE [LBBE] (PEGASE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Virus, mmunité innée et trafic vésiculaire - Vesicular trafficking, innate response and viruses (VIV), Grass, Vincent [0000-0001-7710-4789], Talemi, Soheil Rastgou [0000-0002-9999-2403], Décembre, Elodie [0000-0001-6891-6320], Kohl, Alain [0000-0002-1523-9458], Muñoz-González, Sara [0000-0002-7846-7001], Sherry, Lee [0000-0002-4367-772X], Höfer, Thomas [0000-0003-3560-8780], Boussau, Bastien [0000-0003-0776-4460], Dreux, Marlène [0000-0002-6607-4796], and Apollo - University of Cambridge Repository
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Infectivity ,Experimental evolution ,Zika Virus Infection ,[SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE] ,Medicine (miscellaneous) ,Zika Virus ,Biology ,biology.organism_classification ,Phenotype ,Virology ,Antiviral Agents ,Virus ,General Biochemistry, Genetics and Molecular Biology ,Zika virus ,Toll-Like Receptor 3 ,Viral replication ,Interferon ,Viral evolution ,medicine ,Humans ,Interferons ,General Agricultural and Biological Sciences ,medicine.drug - Abstract
Zika virus (ZIKV) infection can cause developmental and neurological defects and represents a threat for human health. Type I/III interferon responses control ZIKV infection and pathological processes, yet the virus has evolved various mechanisms to defeat these host responses. Here, we established a pipeline to delineate at high-resolution the genetic evolution of ZIKV in a controlled host cell environment. We uncovered that serially passaged ZIKV acquired increased infectivity, defined as the probability for one virus to initiate infection, and simultaneously developed a resistance to TLR3-induced restriction. We built a mathematical model that suggests that the increased infectivity is due to a reduced time-lag between infection and viral replication. We found that this adaptation is cell-type specific, suggesting that different cell environments may drive viral evolution along different routes. Deep-sequencing of ZIKV quasi-species pinpointed mutations whose increased frequencies temporally coincide with the acquisition of the adapted phenotype. We functionally validated a point-mutation in ZIKV envelope (E) protein recapitulating the adapted phenotype. Its positioning on the E structure suggests a putative function in protein refolding/stability. Altogether, our results uncovered ZIKV adaptations to the cell environment leading to an accelerated replication onset coupled with resistance to TLR3-induced antiviral response. Our work provides insights into viral escape mechanisms and interactions with host cell and can serve as a framework to study other viruses.
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- 2020
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8. Plasmacytoid Dendritic Cells and Infected Cells Form an Interferogenic Synapse Required for Antiviral Responses
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Marlène Dreux, Séverin Coléon, Lee Sherry, Elodie Décembre, Congcong Dong, Brian Webster, Sonia Assil, Omran Allatif, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CCSD, Accord Elsevier, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
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Hepatitis C virus ,[SDV]Life Sciences [q-bio] ,Endocytic cycle ,Integrin ,Hepacivirus ,Dengue virus ,medicine.disease_cause ,Microbiology ,Antiviral Agents ,Virus ,Cell Line ,Synapse ,03 medical and health sciences ,0302 clinical medicine ,Interferon ,Virology ,medicine ,Cell Adhesion ,Humans ,Immunologic Factors ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,0303 health sciences ,biology ,hemic and immune systems ,TLR7 ,Dendritic Cells ,Zika Virus ,Dengue Virus ,Intercellular Adhesion Molecule-1 ,Coculture Techniques ,Immunity, Innate ,Lymphocyte Function-Associated Antigen-1 ,3. Good health ,Cell biology ,[SDV] Life Sciences [q-bio] ,Toll-Like Receptor 7 ,Virus Diseases ,Interferon Type I ,biology.protein ,Parasitology ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Type I interferon (IFN-I) is critical for antiviral defense, and plasmacytoid dendritic cells (pDCs) are a predominant source of IFN-I during virus infection. pDC-mediated antiviral responses are stimulated upon physical contact with infected cells, during which immunostimulatory viral RNA is transferred to pDCs, leading to IFN production via the nucleic acid sensor TLR7. Using dengue, hepatitis C, and Zika viruses, we demonstrate that the contact site of pDCs with infected cells is a specialized platform we term the interferogenic synapse, which enables viral RNA transfer and antiviral responses. This synapse is formed via αLβ2 integrin-ICAM-1 adhesion complexes and the recruitment of the actin network and endocytic machinery. TLR7 signaling in pDCs promotes interferogenic synapse establishment and provides feed-forward regulation, sustaining pDC contacts with infected cells. This interferogenic synapse may allow pDCs to scan infected cells and locally secrete IFN-I, thereby confining a potentially deleterious response.
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- 2019
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9. Immature particles and capsid-free viral RNA produced by Yellow fever virus-infected cells stimulate plasmacytoid dendritic cells to secrete interferons
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Jean-Philippe Herbeuval, Annette Martin, Nikaïa Smith, Marlène Dreux, Ségolène Gracias, Laura Sinigaglia, Nolwenn Jouvenet, Elodie Décembre, Matthieu Fritz, Frédéric Tangy, Daniela Bruni, Génomique virale et vaccination, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Trafic Vésiculaire, Réponse Innée et Virus – Vesicular trafficking, Innate response, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique moléculaire des virus à ARN, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), We thank the following funding agencies: Agence Nationale pour la Recherche (ANR-12-JSV3-003-01, ANR-16-CE15-0025-01), Ville de Paris EMERGENCES Program, Marie Curie International Reintegration program PCIG11-GA-2012-322060, Centre National de la Recherche Scientifique (CNRS), Institut Pasteur and the EMBO YIP program. L.S. was supported by the Pasteur Paris University (PPU) International PhD program through an ‘Institut Carnot Pasteur Maladies Infectieuses’ grant. M.F. was the recipient of a Université Paris Diderot PhD fellowship, ANR-12-JSV3-0003,Viropero,Modulation spatiale et temporelle de la réponse antivirale MAVS(2012), ANR-16-CE15-0025,Viro-Storm,Mécanismes de production incontrôlée de cytokines au cours de l'infection virale(2016), European Project: 322060,EC:FP7:PEOPLE,FP7-PEOPLE-2012-CIG,VIROPERO(2012), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), ANR-16-CE15-0025,Viro-Storm,Mécanismes de production incontrôlée de cytokines au cours de l’infection virale(2016), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), jouvenet, nolwenn, Jeunes Chercheuses et Jeunes Chercheurs - Modulation spatiale et temporelle de la réponse antivirale MAVS - - Viropero2012 - ANR-12-JSV3-0003 - JC - VALID, Mécanismes de production incontrôlée de cytokines au cours de l'infection virale - - Viro-Storm2016 - ANR-16-CE15-0025 - AAPG2016 - VALID, and TEMPORAL AND SPATIAL MODULATION OF ANTIVIRAL MAVS SIGNALING - VIROPERO - - EC:FP7:PEOPLE2012-08-01 - 2016-07-31 - 322060 - VALID
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0301 basic medicine ,Adult ,Male ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,Hepatitis C virus ,viruses ,lcsh:Medicine ,Dengue virus ,medicine.disease_cause ,Virus ,Article ,03 medical and health sciences ,Flaviviridae ,Young Adult ,Capsid ,Yellow Fever ,medicine ,Humans ,lcsh:Science ,Cells, Cultured ,Aged ,[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Multidisciplinary ,biology ,lcsh:R ,Virion ,RNA ,hemic and immune systems ,TLR7 ,Dendritic Cells ,Middle Aged ,biology.organism_classification ,Virology ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,3. Good health ,Flavivirus ,030104 developmental biology ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,biology.protein ,RNA, Viral ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,lcsh:Q ,Female ,Interferons ,Antibody ,[SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,Yellow fever virus - Abstract
Plasmacytoid dendritic cells (pDCs) are specialized in the production of interferons (IFNs) in response to viral infections. The Flaviviridae family comprises enveloped RNA viruses such as Hepatitis C virus (HCV) and Dengue virus (DENV). Cell-free flaviviridae virions poorly stimulate pDCs to produce IFN. By contrast, cells infected with HCV and DENV potently stimulate pDCs via short-range delivery of viral RNAs, which are either packaged within immature virions or secreted exosomes. We report that cells infected with Yellow fever virus (YFV), the prototypical flavivirus, stimulated pDCs to produce IFNs in a TLR7- and cell contact- dependent manner. Such stimulation was unaffected by the presence of YFV neutralizing antibodies. As reported for DENV, cells producing immature YFV particles were more potent at stimulating pDCs than cells releasing mature virions. Additionally, cells replicating a release-deficient YFV mutant or a YFV subgenomic RNA lacking structural protein-coding sequences participated in pDC stimulation. Thus, viral RNAs produced by YFV-infected cells reach pDCs via at least two mechanisms: within immature particles and as capsid-free RNAs. Our work highlights the ability of pDCs to respond to a variety of viral RNA-laden carriers generated from infected cells.
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- 2018
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10. Antiviral Response by Plasmacytoid Dendritic Cells via Interferogenic Synapse with Infected Cells
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Brian Webster, Omran Allatif, Séverin Coléon, Sonia Assil, Elodie Décembre, Marlène Dreux, and Lee Sherry
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hemic and immune systems ,Biology ,medicine.disease ,Endocytosis ,Dengue fever ,Cell biology ,Synapse ,Interferon ,medicine ,Secretion ,Receptor ,Actin ,Function (biology) ,medicine.drug - Abstract
SummaryType I interferon (IFN-I) is critical for protection against viral infections. Plasmacytoid dendritic cells (pDCs) massively produce IFN-I against viruses. Physical contacts are required for pDC-mediated sensing of cells infected by genetically distant viruses. How and why these contacts are established remains enigmatic. Using dengue, hepatitis C, zika viruses, we demonstrate that the pDC/infected cell interface is a specialized platform for viral immunostimulatory-RNA transfer, which we named interferogenic synapse and required for pDC-mediated antiviral response. This synapse is an exquisitely differentiated territory with polarized adhesion complexes and regulators of actin network and endocytosis. Toll-like receptor 7-induced signaling in pDCs promotes the interferogenic synapse establishment, thus providing a feed-forward regulation that sustains contacts with infected cells. We propose that the interferogenic synapse is crucial to pDC function as it allows scanning of infected cells to locally secrete IFN-I at the infection site, thereby confining a response potentially deleterious to the host.HighlightspDCs adhere to infected cells via αLβ2 integrin/ICAM-1Regulators of actin network and endocytosis polarize at contactTLR7-induced signaling potentiates pDC polarityInfected cells activate pDCs by interferogenic synapse
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- 2018
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11. Author response: Plasmacytoid dendritic cells control dengue and Chikungunya virus infections via IRF7-regulated interferon responses
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Matthew L. Albert, Isabelle Bouvier, Biljana Zafirova, Darragh Duffy, Pierre-Emmanuel Joubert, Scott W Werneke, Thierry Walzer, Elodie Décembre, Marlène Dreux, Séverin Coléon, Helena Paidassi, Sebastien This, and Brian Webster
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0301 basic medicine ,Biology ,medicine.disease ,medicine.disease_cause ,Virology ,Virus ,Dengue fever ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Interferon ,medicine ,IRF7 ,Chikungunya ,030215 immunology ,medicine.drug - Published
- 2018
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12. Les exosomes
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Elodie Décembre, Sonia Assil, and Marlène Dreux
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0303 health sciences ,biology ,Hepacivirus ,RNA ,General Medicine ,biology.organism_classification ,Virology ,General Biochemistry, Genetics and Molecular Biology ,Microvesicles ,03 medical and health sciences ,0302 clinical medicine ,Immunization ,Viral immunology ,030217 neurology & neurosurgery ,030304 developmental biology - Published
- 2013
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13. Sensing of immature particles produced by dengue virus infected cells induces an antiviral response by plasmacytoid dendritic cells
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Andrew D. Davidson, Elodie Décembre, Sonia Assil, Gavin R. Screaton, Marlène Dreux, Juthathip Mongkolsapaya, Wanwisa Dejnirattisai, Marine L. B. Hillaire, Naiglin, Laurence, Virologie humaine, École normale supérieure de Lyon (ENS de Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), and École normale supérieure - Lyon (ENS Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM)
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lcsh:Immunologic diseases. Allergy ,[SDV]Life Sciences [q-bio] ,viruses ,Immunology ,Dengue virus ,medicine.disease_cause ,Membrane Fusion ,Microbiology ,Virus ,Cell Line ,03 medical and health sciences ,Viral envelope ,Viral Envelope Proteins ,Virology ,Emerging Viral Diseases ,Genetics ,medicine ,Humans ,Molecular Biology ,lcsh:QH301-705.5 ,030304 developmental biology ,0303 health sciences ,Innate Immune System ,Innate immune system ,biology ,030306 microbiology ,Immunity ,virus diseases ,Biology and Life Sciences ,hemic and immune systems ,TLR7 ,Dendritic Cells ,Dengue Virus ,biology.organism_classification ,Actin cytoskeleton ,Biological Evolution ,Immunity, Innate ,3. Good health ,[SDV] Life Sciences [q-bio] ,Flavivirus ,Actin Cytoskeleton ,lcsh:Biology (General) ,Immune System ,Parasitology ,Cytokine secretion ,lcsh:RC581-607 ,Research Article - Abstract
Dengue virus (DENV) is the leading cause of mosquito-borne viral illness and death in humans. Like many viruses, DENV has evolved potent mechanisms that abolish the antiviral response within infected cells. Nevertheless, several in vivo studies have demonstrated a key role of the innate immune response in controlling DENV infection and disease progression. Here, we report that sensing of DENV infected cells by plasmacytoid dendritic cells (pDCs) triggers a robust TLR7-dependent production of IFNα, concomitant with additional antiviral responses, including inflammatory cytokine secretion and pDC maturation. We demonstrate that unlike the efficient cell-free transmission of viral infectivity, pDC activation depends on cell-to-cell contact, a feature observed for various cell types and primary cells infected by DENV, as well as West Nile virus, another member of the Flavivirus genus. We show that the sensing of DENV infected cells by pDCs requires viral envelope protein-dependent secretion and transmission of viral RNA. Consistently with the cell-to-cell sensing-dependent pDC activation, we found that DENV structural components are clustered at the interface between pDCs and infected cells. The actin cytoskeleton is pivotal for both this clustering at the contacts and pDC activation, suggesting that this structural network likely contributes to the transmission of viral components to the pDCs. Due to an evolutionarily conserved suboptimal cleavage of the precursor membrane protein (prM), DENV infected cells release uncleaved prM containing-immature particles, which are deficient for membrane fusion function. We demonstrate that cells releasing immature particles trigger pDC IFN response more potently than cells producing fusion-competent mature virus. Altogether, our results imply that immature particles, as a carrier to endolysosome-localized TLR7 sensor, may contribute to regulate the progression of dengue disease by eliciting a strong innate response., Author Summary Viral recognition by the host often triggers an antiviral state, which suppresses viral spread and imparts adaptive immunity. Like many viruses, dengue virus (DENV) defeats the host-sensing pathway within infected cells. However, in vivo studies have demonstrated a key role of innate immunity in controlling DENV infection. Here we report that sensing of DENV-infected cells by non-permissive innate immune cells, the plasmacytoid dendritic cells (pDCs), triggers a cell-contact- and TLR7-dependent activation of a strong antiviral IFN response. This cell-to-cell sensing involves transmission of viral elements that are clustered at the interface between pDCs and infected cells and is regulated by the actin network. Importantly, we revealed that uncleaved prM surface protein-containing immature particles play a key function in stimulating the innate immune response. These non-infectious immature particles are released by infected cells as a consequence of a suboptimal cleavage site, which is an evolutionarily conserved viral feature that likely favors the export of infectious virus by prevention of premature membrane fusion in the secretory pathway. Therefore our results highlight a conceptually novel trade-off between efficient infectious virus release and the production of IFN-inducing particles. This concept may have broad importance for the many viruses that, like DENV, can disable the pathogen-sensing machinery within infected cells and can release uncleaved glycoprotein-containing non-infectious particles.
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- 2014
14. Short range exosomal transfer of viral RNA from infected cells to plasmacytoid dendritic cells triggers innate immunity
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Stefan Wieland, Francis V. Chisari, Marlène Dreux, Bryan Boyd, Urtzi Garaigorta, Elodie Décembre, Josan Chung, Christina Whitten-Bauer, Virus, mmunité innée et trafic vésiculaire - Vesicular trafficking, innate response and viruses (VIV), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), The Scripps Research Institute [La Jolla, San Diego], Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), The Scripps Research Institute [La Jolla], University of California [San Diego] (UC San Diego), University of California-University of California, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Cancer Research ,Endosome ,[SDV]Life Sciences [q-bio] ,Hepacivirus ,Biology ,Exosomes ,Microbiology ,Exosome ,ESCRT ,Article ,03 medical and health sciences ,0302 clinical medicine ,Interferon ,Immunology and Microbiology(all) ,Virology ,medicine ,Humans ,Molecular Biology ,Cells, Cultured ,030304 developmental biology ,0303 health sciences ,Innate immune system ,RNA ,TLR7 ,Dendritic Cells ,Microvesicles ,Immunity, Innate ,3. Good health ,Cell biology ,030220 oncology & carcinogenesis ,Hepatocytes ,RNA, Viral ,Parasitology ,medicine.drug - Abstract
SummaryViral nucleic acids often trigger an innate immune response in infected cells. Many viruses, including hepatitis C virus (HCV), have evolved mechanisms to evade intracellular recognition. Nevertheless, HCV-permissive cells can trigger a viral RNA-, TLR7-, and cell-contact-dependent compensatory interferon response in nonpermissive plasmacytoid dendritic cells (pDCs). Here we report that these events are mediated by transfer of HCV-RNA-containing exosomes from infected cells to pDCs. The exosomal viral RNA transfer is dependent on the endosomal sorting complex required for transport (ESCRT) machinery and on Annexin A2, an RNA-binding protein involved in membrane vesicle trafficking, and is suppressed by exosome release inhibitors. Further, purified concentrated HCV-RNA-containing exosomes are sufficient to activate pDCs. Thus, vesicular sequestration and exosomal export of viral RNA may serve both as a viral strategy to evade pathogen sensing within infected cells and as a host strategy to induce an unopposed innate response in replication-nonpermissive bystander cells.
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- 2012
- Full Text
- View/download PDF
15. ERK1 Regulates the Hematopoietic Stem Cell Niches
- Author
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Françoise Porteu, Elodie Décembre, Vincent Feuillet, Soizic Guihard, Jacques Pouysségur, Pierre Jurdic, Gilles Pagès, Nathalie Saulnier, Xavier Holy, Denis Clay, Murielle Gaudry, Université Paris Descartes - Paris 5 (UPD5), 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), Institut de Recherche Biomédicale des Armées (IRBA), Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Nice Sophia-Antipolis (UNSA), Agence Nationale pour la Recherche [ANR-08-BLAN-0332], Ministere de l'Enseignement Superieur et de la Recherche, Institut National de la sante et de la recherche medicale (INSERM), Association pour la Recherche contre le Cancer [SFI20101201698], Ligue Contre le Cancer, comite d'Ile de France [RS11/75-24], Institut National du Cancer (CSHLE) [2008 INCa], ProdInra, Migration, Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-École normale supérieure - Lyon (ENS Lyon)
- Subjects
Myeloid ,Cellular differentiation ,[SDV]Life Sciences [q-bio] ,lcsh:Medicine ,Monocytes ,ACTIVATION ,Mice ,0302 clinical medicine ,Bone Density ,Bone Marrow ,Cell Movement ,Osteogenesis ,Bone cell ,Molecular Cell Biology ,Stem Cell Niche ,lcsh:Science ,0303 health sciences ,Multidisciplinary ,Mitogen-Activated Protein Kinase 3 ,Stem Cells ,OSTEOCLASTS ,Hematopoietic stem cell ,Cell Differentiation ,Animal Models ,COLONY-STIMULATING FACTOR ,Signaling Cascades ,Cell biology ,[SDV] Life Sciences [q-bio] ,Haematopoiesis ,medicine.anatomical_structure ,DIFFERENTIATION ,Cellular Microenvironment ,MYELOLINEAGE COMMITMENT ,PROTEIN-KINASE PATHWAY ,MAP KINASE ,KNOCKOUT MICE ,BONE ,RECEPTOR ,Research Article ,Signal Transduction ,Biology ,[INFO] Computer Science [cs] ,Bone and Bones ,03 medical and health sciences ,Model Organisms ,medicine ,Animals ,Cell Lineage ,[INFO]Computer Science [cs] ,Progenitor cell ,030304 developmental biology ,Cell Proliferation ,Osteoblasts ,Macrophages ,lcsh:R ,Molecular Development ,Hematopoietic Stem Cells ,Cell Compartmentation ,Mice, Inbred C57BL ,lcsh:Q ,Bone marrow ,030217 neurology & neurosurgery ,Gene Deletion ,Homing (hematopoietic) ,Developmental Biology - Abstract
International audience; The mitogen-activated protein kinases (MAPK) ERK1 and ERK2 are among the major signal transduction molecules but little is known about their specific functions in vivo. ERK activity is provided by two isoforms, ERK1 and ERK2, which are ubiquitously expressed and share activators and substrates. However, there are not in vivo studies which have reported a role for ERK1 or ERK2 in HSCs and the bone marrow microenvironment. The present study shows that the ERK1-deficient mice present a mild osteopetrosis phenotype. The lodging and the homing abilities of the ERK1(-/-) HSC are impaired, suggesting that the ERK1(-/-)-defective environment may affect the engrafment of HSCs. Serial transplantations demonstrate that ERK1 is involved in the maintenance of an appropriate medullar microenvironment, but that the intrinsic properties of HSCs are not altered by the ERK1(-/-) defective microenvironment. Deletion of ERK1 impaired in vitro and in vivo osteoclastogenesis while osteoblasts were unaffected. As osteoclasts derive from precursors of the monocyte/macrophage lineage, investigation of the monocytic compartment was performed. In vivo analysis of the myeloid lineage progenitors revealed that the frequency of CMPs increased by approximately 1.3-fold, while the frequency of GMPs significantly decreased by almost 2-fold, compared with the respective WT compartments. The overall mononuclear-phagocyte lineage development was compromised in these mice due to a reduced expression of the M-CSF receptor on myeloid progenitors. These results show that the cellular targets of ERK1 are M-CSFR-responsive cells, upstream to osteoclasts. While ERK1 is well known to be activated by M-CSF, the present results are the first to point out an ERK1-dependent M-CSFR regulation on hematopoietic progenitors. This study reinforces the hypothesis of an active cross-talk between HSCs, their progeny and bone cells in the maintenance of the homeostasis of these compartments.
- Published
- 2012
- Full Text
- View/download PDF
16. Interference with the production of infectious viral particles and bimodal inhibition of replication are broadly conserved antiviral properties of IFITMs.
- Author
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Kevin Tartour, Xuan-Nhi Nguyen, Romain Appourchaux, Sonia Assil, Véronique Barateau, Louis-Marie Bloyet, Julien Burlaud Gaillard, Marie-Pierre Confort, Beatriz Escudero-Perez, Henri Gruffat, Saw See Hong, Marie Moroso, Olivier Reynard, Stéphanie Reynard, Elodie Decembre, Najate Ftaich, Axel Rossi, Nannan Wu, Frédérick Arnaud, Sylvain Baize, Marlène Dreux, Denis Gerlier, Glaucia Paranhos-Baccala, Viktor Volchkov, Philippe Roingeard, and Andrea Cimarelli
- Subjects
Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
IFITMs are broad antiviral factors that block incoming virions in endosomal vesicles, protecting target cells from infection. In the case of HIV-1, we and others reported the existence of an additional antiviral mechanism through which IFITMs lead to the production of virions of reduced infectivity. However, whether this second mechanism of inhibition is unique to HIV or extends to other viruses is currently unknown. To address this question, we have analyzed the susceptibility of a broad spectrum of viruses to the negative imprinting of the virion particles infectivity by IFITMs. The results we have gathered indicate that this second antiviral property of IFITMs extends well beyond HIV and we were able to identify viruses susceptible to the three IFITMs altogether (HIV-1, SIV, MLV, MPMV, VSV, MeV, EBOV, WNV), as well as viruses that displayed a member-specific susceptibility (EBV, DUGV), or were resistant to all IFITMs (HCV, RVFV, MOPV, AAV). The swapping of genetic elements between resistant and susceptible viruses allowed us to point to specificities in the viral mode of assembly, rather than glycoproteins as dominant factors of susceptibility. However, we also show that, contrarily to X4-, R5-tropic HIV-1 envelopes confer resistance against IFITM3, suggesting that viral receptors add an additional layer of complexity in the IFITMs-HIV interplay. Lastly, we show that the overall antiviral effects ascribed to IFITMs during spreading infections, are the result of a bimodal inhibition in which IFITMs act both by protecting target cells from incoming viruses and in driving the production of virions of reduced infectivity. Overall, our study reports for the first time that the negative imprinting of the virion particles infectivity is a conserved antiviral property of IFITMs and establishes IFITMs as a paradigm of restriction factor capable of interfering with two distinct phases of a virus life cycle.
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- 2017
- Full Text
- View/download PDF
17. ERK1 regulates the hematopoietic stem cell niches.
- Author
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Nathalie Saulnier, Soizic Guihard, Xavier Holy, Elodie Decembre, Pierre Jurdic, Denis Clay, Vincent Feuillet, Gilles Pagès, Jacques Pouysségur, Françoise Porteu, and Murielle Gaudry
- Subjects
Medicine ,Science - Abstract
The mitogen-activated protein kinases (MAPK) ERK1 and ERK2 are among the major signal transduction molecules but little is known about their specific functions in vivo. ERK activity is provided by two isoforms, ERK1 and ERK2, which are ubiquitously expressed and share activators and substrates. However, there are not in vivo studies which have reported a role for ERK1 or ERK2 in HSCs and the bone marrow microenvironment. The present study shows that the ERK1-deficient mice present a mild osteopetrosis phenotype. The lodging and the homing abilities of the ERK1(-/-) HSC are impaired, suggesting that the ERK1(-/-)-defective environment may affect the engrafment of HSCs. Serial transplantations demonstrate that ERK1 is involved in the maintenance of an appropriate medullar microenvironment, but that the intrinsic properties of HSCs are not altered by the ERK1(-/-) defective microenvironment. Deletion of ERK1 impaired in vitro and in vivo osteoclastogenesis while osteoblasts were unaffected. As osteoclasts derive from precursors of the monocyte/macrophage lineage, investigation of the monocytic compartment was performed. In vivo analysis of the myeloid lineage progenitors revealed that the frequency of CMPs increased by approximately 1.3-fold, while the frequency of GMPs significantly decreased by almost 2-fold, compared with the respective WT compartments. The overall mononuclear-phagocyte lineage development was compromised in these mice due to a reduced expression of the M-CSF receptor on myeloid progenitors. These results show that the cellular targets of ERK1 are M-CSFR-responsive cells, upstream to osteoclasts. While ERK1 is well known to be activated by M-CSF, the present results are the first to point out an ERK1-dependent M-CSFR regulation on hematopoietic progenitors. This study reinforces the hypothesis of an active cross-talk between HSCs, their progeny and bone cells in the maintenance of the homeostasis of these compartments.
- Published
- 2012
- Full Text
- View/download PDF
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