Search

Your search keyword '"Equipe Chimie et Biologie"' showing total 12 results
Start Over Author "Equipe Chimie et Biologie"
12 results on '"Equipe Chimie et Biologie"'

1. FHL1 is a major host factor for chikungunya virus infection

Author

Cécile Doyen, Thérèse Couderc, Alexis Brugier, R. Juntas-Morales, Philippe Roingeard, Rabah Ben Yaou, Julien Burlaud-Gaillard, Etienne Simon-Loriere, Mohamed Lamine Hafirassou, Sophia Rafasse, Vasiliya Kril, Pierre-Olivier Vidalain, Laura Pezzi, Gisèle Bonne, Lucie Gueneau, Xavier de Lamballerie, Marc Lecuit, Laurent Meertens, Anne Bertrand-Legout, Beate M. Kümmerer, Ali Amara, Lucie Bonnet-Madin, Thibaud Goupil, Constance Delaugerre, Athena Labeau, Monsef Benkirane, Génomes, biologie cellulaire et thérapeutiques (GenCellDi (UMR_S_944)), Collège de France (CdF (institution))-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Biologie des Infections - Biology of Infection, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute of Virology [Bonn, Germany], University of Bonn Medical Centre, Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Institut Pasteur [Paris] (IP), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Equipe Chimie et Biologie, Modélisation et Immunologie pour la Thérapie (CBMIT), Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5), Génomique virale et vaccination, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Laboratoire de Virologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de maladies infectieuses et tropicales [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service des Maladies infectieuses et tropicales [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This study received funding from the French Government’s Investissement d’Avenir program, Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (ANR-10-LABX-62-IBEID), the ‘Investissements d’Avenir’ program (ANR-10-IHUB-0002, ANR-15-CE15-00029 ZIKAHOST and the INCEPTION program ANR-16-CONV-0005), Institut Pasteur, Inserm and European Research Council. Viruses were provided by the Europe and Virus Archive, which has received funding from the EU Horizon 2020 research and innovation program under grant agreement 653316. The authors thank the EA7310, Laboratoire de Virologie, Université de Corse-Inserm for funding the doctoral position of L.P., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-17-CE15-0029,ZIKAHOST,LES FACTEURS DE L'HÔTE ASSOCIÉS À LA NEUROPATHOGÉNICITÉ DU VIRUS ZIKA(2017), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), Institut National de la Santé et de la Recherche Médicale (INSERM)-Collège de France (CdF (institution))-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris], Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Myologie, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Aix Marseille Université (AMU)-Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), BUISINE, Soline, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, LES FACTEURS DE L'HÔTE ASSOCIÉS À LA NEUROPATHOGÉNICITÉ DU VIRUS ZIKA - - ZIKAHOST2017 - ANR-17-CE15-0029 - AAPG2017 - VALID, and Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs - - INCEPTION2016 - ANR-16-CONV-0005 - CONV - VALID

Subjects
Male, Permissiveness, viruses, Viral pathogenesis, Muscle Proteins, Host-Derived Cellular Factors, Alphavirus, Viral Nonstructural Proteins, Virus Replication, medicine.disease_cause, Virus, Myoblasts, Mice, 03 medical and health sciences, medicine, Animals, Humans, O'nyong-nyong Virus, Chikungunya, Cells, Cultured, 030304 developmental biology, Host factor, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, Multidisciplinary, biology, 030306 microbiology, Intracellular Signaling Peptides and Proteins, virus diseases, Fibroblasts, LIM Domain Proteins, biology.organism_classification, Virology, FHL1, 3. Good health, HEK293 Cells, Viral replication, Host-Pathogen Interactions, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Chikungunya Fever, RNA, Viral, Female, Chikungunya virus, Protein Binding
Abstract

Chikungunya virus (CHIKV) is a re-emerging alphavirus that is transmitted to humans by mosquito bites and causes musculoskeletal and joint pain1,2. Despite intensive investigations, the human cellular factors that are critical for CHIKV infection remain unknown, hampering the understanding of viral pathogenesis and the development of anti-CHIKV therapies. Here we identified the four-and-a-half LIM domain protein 1 (FHL1)3 as a host factor that is required for CHIKV permissiveness and pathogenesis in humans and mice. Ablation of FHL1 expression results in the inhibition of infection by several CHIKV strains and o’nyong-nyong virus, but not by other alphaviruses and flaviviruses. Conversely, expression of FHL1 promotes CHIKV infection in cells that do not normally express it. FHL1 interacts directly with the hypervariable domain of the nsP3 protein of CHIKV and is essential for the replication of viral RNA. FHL1 is highly expressed in CHIKV-target cells and is particularly abundant in muscles3,4. Dermal fibroblasts and muscle cells derived from patients with Emery–Dreifuss muscular dystrophy that lack functional FHL15 are resistant to CHIKV infection. Furthermore, CHIKV infection is undetectable in Fhl1-knockout mice. Overall, this study shows that FHL1 is a key factor expressed by the host that enables CHIKV infection and identifies the interaction between nsP3 and FHL1 as a promising target for the development of anti-CHIKV therapies. FHL1 is a key factor expressed by humans and mice that is required for chikungunya virus infection and is therefore a promising target for the development of therapies against chikungunya virus.

Published
2019

2. Screening and evaluation of antiviral compounds against Equid alpha-herpesviruses using an impedance-based cellular assay

Author

Pierre-Hugues Pitel, Aymeric Hans, Côme Thieulent, Christine Fortier, Erika Hue, Guillaume Fortier, Stéphan Zientara, Patrick Dallemagne, Stéphane Pronost, Pierre-Olivier Vidalain, Hélène Munier-Lehmann, LABÉO, Pôle d’analyses et de recherche de Normandie (LABÉO), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), ImpedanCELL, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Virologie UMR1161 (VIRO), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire d'Alfort (ENVA), Chimie et Biocatalyse, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Unité de virologie et parasitologie équine, Laboratoire de pathologie équine de Dozulé, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Equipe Chimie et Biologie, Modélisation et Immunologie pour la Thérapie (CBMIT), Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), This work was supported by LABÉO, IFCE (Institut Français du Cheval et de l′Equitation, project AMIE), Fonds Eperon (project N87-2014, N07-2015, N07-2016 and N13-2017) and Région Normandie (CPER R25 P3)., Interactions Cellules Organismes Environnement (ICORE), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-CHU Caen, Normandie Université (NU), Institut National de la Recherche Agronomique (INRA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-École nationale vétérinaire d'Alfort (ENVA), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de santé animale, sites de Maisons-Alfort et de Normandie, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Laboratoire de santé animale, sites de Maisons-Alfort et de Normandie, École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)

Subjects
Ganciclovir, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Population, Alpha (ethology), Cell analysis, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Spironolactone, Biology, Antiviral Agents, Equid herpesviruses, NERVOUS DISORDERS, Cell Line, Real-time cell analysis, 03 medical and health sciences, Cytopathogenic Effect, Viral, xCELLigence, Virology, Electric Impedance, medicine, Lack of efficacy, Animals, Horses, Aciclovir, Antiviral, education, 030304 developmental biology, 0303 health sciences, education.field_of_study, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, Cellular Assay, 030302 biochemistry & molecular biology, Impedance, Herpesviridae Infections, High-Throughput Screening Assays, 3. Good health, Screening, Herpesvirus 3, Equid, Herpesvirus 4, Equid, Herpesvirus 1, Equid, medicine.drug
Abstract

International audience; Equid alpha-herpesviruses (EHV) are responsible for different diseases in equine population. EHV-1 causes respiratory diseases, abortions and nervous disorders, EHV-4 causes respiratory diseases and sporadic abortion, while EHV-3 is responsible of equine coital exanthema. In view of the lack of efficacy of vaccines against EHV-1 and EHV-4 and in the absence of vaccines against EHV-3, the use of antiviral treatment is of great interest. In this study, we documented the interest of the Real-Time Cell Analysis (RTCA) technology to monitor the cytopathic effects induced by these viruses on equine dermal cells, and established the efficacy of this method to evaluate the antiviral effect of aciclovir (ACV) and ganciclovir (GCV). In addition, the RTCA technology has also been found appropriate for the high-throughput screening of small molecules against EHV, allowing the identification of spironolactone as a novel antiviral against EHV.

Published
2019

3. TRIM8 is required for virus-induced IFN response in human plasmacytoid dendritic cells

Author

Olivier Moncorgé, Sarah Maillet, Jean-Philippe Herbeuval, Nikaïa Smith, Joanne Edouard, Ghizlane Maarifi, Nathalie J. Arhel, Jean-Pierre Levraud, Frédéric Sohm, Georges Lutfalla, Fabien Blanchet, Sébastien Nisole, Célia Chamontin, Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Universitätsklinikum Ulm - University Hospital of Ulm, Equipe Chimie et Biologie, Modélisation et Immunologie pour la Thérapie (CBMIT), Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5), Animaux Modèles Aquatiques : ingéniérie GENétique (AMAGEN), Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), 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), Dynamique des interactions membranaires normales et pathologiques (DIMNP), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1), Macrophages et Développement de l’Immunité, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Funding: This work was supported by Labex EpiGenMed, an Investissements d’avenir program (ANR-10-LABX-12-01 to N.J.A. and S.N.), the Agence National de la Recherche sur le SIDA et les Hépatites virales, ANRS (AO2017-1 to J.-P.H.), the European Community’s Seventh Framework Program (FP7- PEOPLE-2011-ITN) under the Marie-Curie Initial Training Network FishForPharma (PITN-GA-2011-289209 to G.L.), the European Community’s H2020 Program Marie-Curie Innovative Training Network ImageInLife (721537 to G.L. and J.-P.L.), the Agence Nationale de la Recherche (ANR-16-CE20-0002-03 and ANR-10-MDI-009 to J.-P.L.), and the Région Occitanie (REPERE2017ImageInLife to G.L.). G.M. (AO2018-2), N.S. (AO2016-1), O.M. (AO2017-1), and S.M. (AO2017-2) were supported by grants from the ANRS. This work received help and expertise from TACGene, which is supported by the program Investissement d’avenir TEFOR (ANR-II-INSB-0014). N.S. acknowledges support from the European Molecular Biology Organization EMBO for Fellowship (LT-834-2017), the start-up funding program 'Baustein' of the Medical Faculty of Ulm University (LSBN.0147), and the Deutsche Forschungsgemeinschaft DFG (SM 544/1-1)., ANR-10-LABX-0012,EpiGenMed,From Genome and Epigenome to Molecular Medicine: turning new paradigms in biology into the therapeutic strategies of tomorrow(2010), ANR-16-CE20-0002,Fish-RNAvax,Vaccins ARN éco-compatibles pour l'induction de réponses immunitaires protectrices chez le poisson d'élevage(2016), ANR-10-MIDI-0009,ZebraFlam,Signaux et cellules de la réponse inflammatoire: suivi en temps réel chez un vertébré entier, le danio zébré(2010), ANR-11-INBS-0014,TEFOR,Transgenèse pour les Etudes Fonctionnelles sur les Organismes modèles(2011), European Project: 289209,EC:FP7:PEOPLE,FP7-PEOPLE-2011-ITN,FISHFORPHARMA(2012), European Project: 721537,ImageInLife(2017), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), ANR-10-LABX-0012/10-LABX-0012,EpiGenMed,From Genome and Epigenome to Molecular Medicine: turning new paradigms in biology into the therapeutic strategies of tomorrow(2010), ANR: 11-INBS-0014,TEFOR,Transgenèse pour les Etudes Fonctionnelles sur les Organismes modèles(2011), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)

Subjects
Small interfering RNA, Interferon Regulatory Factor-7, Ubiquitin-Protein Ligases, [SDV]Life Sciences [q-bio], Immunology, Regulator, Nerve Tissue Proteins, Cell Line, 03 medical and health sciences, 0302 clinical medicine, Ubiquitin, Interferon, medicine, Animals, Humans, Phosphorylation, RNA, Small Interfering, Research Articles, Zebrafish, 030304 developmental biology, 0303 health sciences, Multidisciplinary, Innate immune system, biology, Influenza A Virus, H3N2 Subtype, SciAdv r-articles, hemic and immune systems, Dendritic Cells, Tripartite motif family, Immunity, Innate, 3. Good health, Cell biology, NIMA-Interacting Peptidylprolyl Isomerase, HEK293 Cells, Interferon Type I, biology.protein, PIN1, HIV-1, IRF7, [SDV.IMM]Life Sciences [q-bio]/Immunology, RNA Interference, Carrier Proteins, Chikungunya virus, 030215 immunology, medicine.drug, Research Article, Signal Transduction
Abstract

TRIM8 and Pin1 oppositely control IRF7-induced interferon production., Plasmacytoid dendritic cells (pDCs) play a crucial role in antiviral innate immunity through their unique capacity to produce large amounts of type I interferons (IFNs) upon viral detection. Tripartite motif (TRIM) proteins have recently come forth as important modulators of innate signaling, but their involvement in pDCs has not been investigated. Here, we performed a rationally streamlined small interfering RNA (siRNA)–based screen of TRIM proteins in human primary pDCs to identify those that are critical for the IFN response. Among candidate hits, TRIM8 emerged as an essential regulator of IFN regulatory factor 7 (IRF7) function. Mechanistically, TRIM8 protects phosphorylated IRF7 (pIRF7) from proteasomal degradation in an E3 ubiquitin ligase–independent manner by preventing its recognition by the peptidyl-prolyl isomerase Pin1. Our findings uncover a previously unknown regulatory mechanism of type I IFN production in pDCs by which TRIM8 and Pin1 oppositely regulate the stability of pIRF7.

Published
2019

4. Sequential actions of EOMES and T-BET promote stepwise maturation of natural killer cells.

Author

Zhang J, Le Gras S, Pouxvielh K, Faure F, Fallone L, Kern N, Moreews M, Mathieu AL, Schneider R, Marliac Q, Jung M, Berton A, Hayek S, Vidalain PO, Marçais A, Dodard G, Dejean A, Brossay L, Ghavi-Helm Y, and Walzer T

Subjects
Animals, Base Sequence, Bone Marrow Cells cytology, Bone Marrow Cells immunology, CD11b Antigen genetics, CD11b Antigen immunology, Cell Cycle drug effects, Cell Cycle immunology, Cell Differentiation, Cell Lineage drug effects, Cell Lineage immunology, Epigenesis, Genetic immunology, Interleukin-12 pharmacology, Killer Cells, Natural cytology, Killer Cells, Natural drug effects, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Promoter Regions, Genetic, Protein Binding, Spleen cytology, Spleen immunology, T-Box Domain Proteins deficiency, T-Box Domain Proteins immunology, Transcription, Genetic, Tumor Necrosis Factor Receptor Superfamily, Member 7 genetics, Tumor Necrosis Factor Receptor Superfamily, Member 7 immunology, Cell Cycle genetics, Cell Lineage genetics, Killer Cells, Natural immunology, T-Box Domain Proteins genetics
Abstract

EOMES and T-BET are related T-box transcription factors that control natural killer (NK) cell development. Here we demonstrate that EOMES and T-BET regulate largely distinct gene sets during this process. EOMES is dominantly expressed in immature NK cells and drives early lineage specification by inducing hallmark receptors and functions. By contrast, T-BET is dominant in mature NK cells, where it induces responsiveness to IL-12 and represses the cell cycle, likely through transcriptional repressors. Regardless, many genes with distinct functions are co-regulated by the two transcription factors. By generating two gene-modified mice facilitating chromatin immunoprecipitation of endogenous EOMES and T-BET, we show a strong overlap in their DNA binding targets, as well as extensive epigenetic changes during NK cell differentiation. Our data thus suggest that EOMES and T-BET may distinctly govern, via differential expression and co-factors recruitment, NK cell maturation by inserting partially overlapping epigenetic regulations., (© 2021. The Author(s).)

Published
2021
Full Text
View/download PDF

5. High Frequency of Viral Co-Detections in Acute Bronchiolitis.

Author

Petat H, Gajdos V, Angoulvant F, Vidalain PO, Corbet S, Marguet C, Brouard J, Vabret A, and Gouilh MA

Subjects
Bronchiolitis, Viral epidemiology, Coinfection epidemiology, Emergency Service, Hospital, France epidemiology, Humans, Infant, Multiplex Polymerase Chain Reaction, Nasopharynx virology, Respiratory Syncytial Virus, Human classification, Respiratory Syncytial Virus, Human genetics, Respiratory Syncytial Virus, Human isolation & purification, Viruses classification, Viruses genetics, Viruses isolation & purification, Bronchiolitis, Viral virology, Coinfection virology
Abstract

Over two years (2012-2014), 719 nasopharyngeal samples were collected from 6-week- to 12-month-old infants presenting at the emergency department with moderate to severe acute bronchiolitis. Viral testing was performed, and we found that 98% of samples were positive, including 90% for respiratory syncytial virus, 34% for human rhino virus, and 55% for viral co-detections, with a predominance of RSV/HRV co-infections (30%). Interestingly, we found that the risk of being infected by HRV is higher in the absence of RSV, suggesting interferences or exclusion mechanisms between these two viruses. Conversely, coronavirus infection had no impact on the likelihood of co-infection involving HRV and RSV. Bronchiolitis is the leading cause of hospitalizations in infants before 12 months of age, and many questions about its role in later chronic respiratory diseases (asthma and chronic obstructive pulmonary disease) exist. The role of virus detection and the burden of viral codetections need to be further explored, in order to understand the physiopathology of chronic respiratory diseases, a major public health issue.

Published
2021
Full Text
View/download PDF

6. Measuring the subcellular compartmentalization of viral infections by protein complementation assay.

Author

Fernandez J, Hassen-Khodja C, Georget V, Rose T, Jacob Y, Janin YL, Nisole S, Vidalain PO, and Arhel NJ

Subjects
Cell Line, Cell Nucleus metabolism, Cytoplasm metabolism, Green Fluorescent Proteins metabolism, HIV Infections metabolism, HeLa Cells, Humans, Nuclear Envelope metabolism, Nuclear Pore metabolism, Ribonucleoproteins metabolism, Virus Replication drug effects, High-Throughput Screening Assays methods, Virus Diseases metabolism, Virus Replication physiology
Abstract

The recent emergence and reemergence of viruses in the human population has highlighted the need to develop broader panels of therapeutic molecules. High-throughput screening assays opening access to untargeted steps of the viral replication cycle will provide powerful leverage to identify innovative antiviral molecules. We report here the development of an innovative protein complementation assay, termed αCentauri, to measure viral translocation between subcellular compartments. As a proof of concept, the Centauri fragment was either tethered to the nuclear pore complex or sequestered in the nucleus, while the complementary α fragment (<16 amino acids) was attached to the integrase proteins of infectious HIV-1. The translocation of viral ribonucleoproteins from the cytoplasm to the nuclear envelope or to the nucleoplasm efficiently reconstituted superfolder green fluorescent protein or NanoLuc αCentauri reporters. These fluorescence- or bioluminescence-based assays offer a robust readout of specific steps of viral infection in a multiwell format that is compatible for high-throughput screening and is validated by a short hairpin RNA-based prototype screen., Competing Interests: Competing interest statement: J.F., S.N., and N.J.A. are inventors on a patent application describing the measurement of protein complementation upon nuclear import as described in this paper.

Published
2021
Full Text
View/download PDF

7. Screening of potential antiviral molecules against equid herpesvirus-1 using cellular impedance measurement: Dataset of 2,891 compounds.

Author

Thieulent C, Fortier C, Munier-Lehmann H, Suzanne P, Dallemagne P, Zientara S, Hans A, Paillot R, Vidalain PO, Pronost S, and Hue E

Abstract

Data presented in this article are associated with the research article "Identification of antiviral compounds against equid herpesvirus-1 using real-time cell assay screening: efficacy of decitabine and valganciclovir alone and in combination" [1]. These data correspond to the in vitro screening of 2,891 potential antiviral compounds against equid herpesvirus-1 (EHV-1) based on impedance measurements using the xCELLigence® RTCA MP System. This dataset includes compounds from three different libraries: i) 1,199 compounds from the Prestwick® Chemical Library, which contains mostly US Food and Drug Administration approved drugs (Prestwick® Chemical, Illkirch, France); ii) 1,651 compounds from the Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN, Caen, France); iii) 41 compounds (called herein in-house antiviral library) selected for their effects against different human viruses. Compounds effective against EHV-1 were selected using the area under normalised curves (AUC n ) and the time required for the Cell Index to decrease by 50% after virus infection (CIT 50 ). The full dataset from the screen is made publicly available for further analyses., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships which have, or could be perceived to have, influenced the work reported in this article., (© 2020 The Authors.)

Published
2020
Full Text
View/download PDF

8. Identification of antiviral compounds against equid herpesvirus-1 using real-time cell assay screening: Efficacy of decitabine and valganciclovir alone or in combination.

Author

Thieulent C, Hue ES, Sutton G, Fortier C, Dallemagne P, Zientara S, Munier-Lehmann H, Hans A, Paillot R, Vidalain PO, and Pronost S

Subjects
Animals, Cell Line, Drug Combinations, Drug Discovery methods, Drug Synergism, Ganciclovir pharmacology, Herpesviridae Infections drug therapy, Herpesviridae Infections virology, High-Throughput Screening Assays methods, Horses, Rabbits, Antiviral Agents pharmacology, Decitabine pharmacology, Herpesviridae Infections veterinary, Herpesvirus 1, Equid drug effects, Valganciclovir pharmacology
Abstract

Equid herpesvirus-1 infections cause respiratory, neurological and reproductive syndromes. Despite preventive treatments with vaccines, resurgence of EHV-1 infection still constitutes a major threat to equine industry. However, no antiviral compound is available to treat infected horses. In this study, 2891 compounds were screened against EHV-1 using impedance measurement. 22 compounds have been found to be effective in vitro against EHV-1. Valganciclovir, ganciclovir, decitabine, aphidicolin, idoxuridine and pritelivir (BAY 57-1293) are the most effective compounds identified, and their antiviral potency was further assessed on E. Derm, RK13 and EEK cells and against 3 different field strains of EHV-1 (ORF30 2254 A/G/C). We also provide evidences of synergistic interactions between valganciclovir and decitabine in our in vitro antiviral assay as determined by MacSynergy II, isobologramm and Chou-Talalay methods. Finally, we showed that deoxycytidine reverts the antiviral effect of decitabine, thus supporting some competition at the level of nucleoside phosphorylation by deoxycytidine kinase and/or DNA synthesis. Deoxycitidine analogues, like decitabine, is a family of compounds identified for the first time with promising antiviral efficacy against herpesviruses., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Published
2020
Full Text
View/download PDF

9. Replication of Equine arteritis virus is efficiently suppressed by purine and pyrimidine biosynthesis inhibitors.

Author

Valle-Casuso JC, Gaudaire D, Martin-Faivre L, Madeline A, Dallemagne P, Pronost S, Munier-Lehmann H, Zientara S, Vidalain PO, and Hans A

Subjects
Animals, Antiviral Agents pharmacology, Arterivirus Infections veterinary, Cell Line, Cytopathogenic Effect, Viral drug effects, Dihydroorotate Dehydrogenase, Horse Diseases virology, Horses genetics, Oxidoreductases Acting on CH-CH Group Donors metabolism, Purines antagonists & inhibitors, Purines biosynthesis, Purines pharmacology, Pyrimidines antagonists & inhibitors, Pyrimidines biosynthesis, Pyrimidines pharmacology, RNA pharmacology, Virus Replication drug effects, Virus Replication physiology, Arterivirus Infections drug therapy, Equartevirus metabolism, Ribavirin pharmacology
Abstract

RNA viruses are responsible for a large variety of animal infections. Equine Arteritis Virus (EAV) is a positive single-stranded RNA virus member of the family Arteriviridae from the order Nidovirales like the Coronaviridae. EAV causes respiratory and reproductive diseases in equids. Although two vaccines are available, the vaccination coverage of the equine population is largely insufficient to prevent new EAV outbreaks around the world. In this study, we present a high-throughput in vitro assay suitable for testing candidate antiviral molecules on equine dermal cells infected by EAV. Using this assay, we identified three molecules that impair EAV infection in equine cells: the broad-spectrum antiviral and nucleoside analog ribavirin, and two compounds previously described as inhibitors of dihydroorotate dehydrogenase (DHODH), the fourth enzyme of the pyrimidine biosynthesis pathway. These molecules effectively suppressed cytopathic effects associated to EAV infection, and strongly inhibited viral replication and production of infectious particles. Since ribavirin is already approved in human and small animal, and that several DHODH inhibitors are in advanced clinical trials, our results open new perspectives for the management of EAV outbreaks.

Published
2020
Full Text
View/download PDF

10. Screening and evaluation of antiviral compounds against Equid alpha-herpesviruses using an impedance-based cellular assay.

Author

Thieulent CJ, Hue ES, Fortier CI, Dallemagne P, Zientara S, Munier-Lehmann H, Hans A, Fortier GD, Pitel PH, Vidalain PO, and Pronost SL

Subjects
Animals, Cell Line, Cytopathogenic Effect, Viral drug effects, Herpesviridae Infections pathology, Herpesviridae Infections virology, Herpesvirus 1, Equid classification, Herpesvirus 3, Equid drug effects, Herpesvirus 4, Equid drug effects, Horses, Spironolactone pharmacology, Antiviral Agents pharmacology, Electric Impedance, Herpesviridae Infections veterinary, Herpesvirus 1, Equid drug effects, High-Throughput Screening Assays methods
Abstract

Equid alpha-herpesviruses (EHV) are responsible for different diseases in equine population. EHV-1 causes respiratory diseases, abortions and nervous disorders, EHV-4 causes respiratory diseases and sporadic abortion, while EHV-3 is responsible of equine coital exanthema. In view of the lack of efficacy of vaccines against EHV-1 and EHV-4 and in the absence of vaccines against EHV-3, the use of antiviral treatment is of great interest. In this study, we documented the interest of the Real-Time Cell Analysis (RTCA) technology to monitor the cytopathic effects induced by these viruses on equine dermal cells, and established the efficacy of this method to evaluate the antiviral effect of aciclovir (ACV) and ganciclovir (GCV). In addition, the RTCA technology has also been found appropriate for the high-throughput screening of small molecules against EHV, allowing the identification of spironolactone as a novel antiviral against EHV., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Published
2019
Full Text
View/download PDF

11. An efficient method for gene silencing in human primary plasmacytoid dendritic cells: silencing of the TLR7/IRF-7 pathway as a proof of concept.

Author

Smith N, Vidalain PO, Nisole S, and Herbeuval JP

Subjects
Dendritic Cells cytology, Electroporation methods, Gene Silencing, Genetic Vectors chemistry, Genetic Vectors metabolism, Humans, Interferon Regulatory Factor-7 genetics, Interferon Regulatory Factor-7 metabolism, Interferon-alpha antagonists & inhibitors, Interferon-alpha metabolism, Lentivirus genetics, Lentivirus metabolism, Polyethyleneimine chemistry, Primary Cell Culture, RNA, Small Interfering genetics, RNA, Small Interfering metabolism, Receptors, CXCR4 genetics, Receptors, CXCR4 metabolism, Toll-Like Receptor 7 genetics, Toll-Like Receptor 7 metabolism, Dendritic Cells metabolism, Fatty Acids, Monounsaturated chemistry, Gene Transfer Techniques, Interferon Regulatory Factor-7 antagonists & inhibitors, Quaternary Ammonium Compounds chemistry, Receptors, CXCR4 antagonists & inhibitors, Toll-Like Receptor 7 antagonists & inhibitors
Abstract

Plasmacytoid dendritic cells (pDC) are specialized immune cells that produce massive levels of type I interferon in response to pathogens. Unfortunately, pDC are fragile and extremely rare, rendering their functional study a tough challenge. However, because of their central role in numerous pathologies, there is a considerable need for an efficient and reproducible protocol for gene silencing in these cells. In this report, we tested six different methods for siRNA delivery into primary human pDC including viral-based, lipid-based, electroporation, and poly-ethylenimine (PEI) technologies. We show that lipid-based reagent DOTAP was extremely efficient for siRNA delivery into pDC, and did not induce cell death or pDC activation. We successfully silenced Toll-Like Receptor 7 (TLR7), CXCR4 and IFN regulatory factor 7 (IRF-7) gene expression in pDC as assessed by RT-qPCR or cytometry. Finally, we showed that TLR7 or IRF-7 silencing in pDC specifically suppressed IFN-α production upon stimulation, providing a functional validation of our transfection protocol.

Published
2016
Full Text
View/download PDF

12. [Plasmacytoid dendritic cells: the novel Eldorado for antiviral therapy?].

Author

Smith N and Herbeuval JP

Subjects
Antigens, Differentiation analysis, Cytotoxicity, Immunologic, Dendritic Cells drug effects, Dendritic Cells metabolism, Endocytosis, HIV physiology, HIV Infections immunology, Humans, Immunity, Innate, Immunophenotyping, Interferon-alpha biosynthesis, Interferon-alpha metabolism, Receptors, TNF-Related Apoptosis-Inducing Ligand immunology, T-Lymphocyte Subsets immunology, TNF-Related Apoptosis-Inducing Ligand immunology, Toll-Like Receptors immunology, Virus Diseases immunology, Virus Replication, Dendritic Cells immunology, Host-Pathogen Interactions immunology, Immunotherapy methods, Virus Diseases therapy
Abstract

Plasmacytoid dendritic cells (pDCs) represent the first line of host defense against viruses and are an essential link between innate and adaptive immunity. The antiviral factor IFN-α is massively produced by pDCs in response to HIV infection and induces the expression of cellular genes that interfere with viral replication (ISG). Indeed, type I IFN produced by pDCs has a direct anti-viral activity against HIV and has important adjuvant function on other immune cell-types, such as T cells, macrophages and dendritic cells. However, the role of type I IFN in HIV disease is complex and may depend on the stage of the disease. The immunologic hallmark of HIV infection is a status of chronic and progressive immune activation, which drives the immune system to exhaustion and leads to severe immunodeficiency. There is now strong evidence that chronic activation of pDCs may promote HIV pathogenesis and have an impact on adaptive T-cell response. Thus, targeting pDCs and type I IFN may open new therapeutic strategies for chronically activated HIV patients., (© Société de Biologie, 2015.)

Published
2015
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results