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3. PAR1 contributes to influenza a virus pathogenicity in mice

Author

Khoufache, Khaled, Berri, Fatma, Nacken, Wolfgang, Vogel, Annette B., Delenne, Marie, Camerer, Eric, Coughlin, Shaun R., Carmeliet, Peter, Lina, Bruno, Rimmelzwaan, Guus F., Planz, Oliver, Ludwig, Stephan, and Riteau, Beatrice

Subjects
Inflammation -- Health aspects -- Risk factors, Influenza -- Complications and side effects -- Care and treatment -- Research -- Health aspects -- Patient outcomes -- Causes of, Thrombin -- Health aspects, Health care industry
Abstract

Influenza causes substantial morbidity and mortality, and highly pathogenic and drug-resistant strains are likely to emerge in the future. Protease-activated receptor 1 (PAR1) is a thrombin-activated receptor that contributes to [...]

Published
2013
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4. PTR Pasteur and partnership conference

Author

Riteau, Beatrice, Département Santé Animale (DEPT SA), Institut National de la Recherche Agronomique (INRA), and ProdInra, Migration

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

National audience

Published
2020

5. From Naproxen Repurposing to Naproxen Analogues and Their Antiviral Activity against Influenza A Virus

Author

Dilly, Sebastien, Fotso, Aurelien Fotso, Lejal, Nathalie, Zedda, Gloria, Chebbo, Mohamad, Rahman, Fryad, Companys, Simon, Bertrand, Helene C., Vidic, Jasmina, Noiray, Magali, Alessi, Marie-Christine, Tarus, Bogdan, Quideau, Stephane, Riteau, Beatrice, Slama-Schwok, Anny, Nutrition, obésité et risque thrombotique (NORT), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre recherche en CardioVasculaire et Nutrition (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de recherche Virologie et Immunologie Moléculaires (VIM), Institut National de la Recherche Agronomique (INRA), Institut des Sciences Moléculaires (ISM), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS Paris)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-ESPCI ParisTech-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-ESPCI ParisTech-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1 (UB)-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Binding Sites, Cyclooxygenase 2 Inhibitors, [SDV]Life Sciences [q-bio], Viral Core Proteins, Drug Repositioning, RNA-Binding Proteins, Nucleocapsid Proteins, Surface Plasmon Resonance, Antiviral Agents, Madin Darby Canine Kidney Cells, Mice, Inbred C57BL, Molecular Docking Simulation, Dogs, Naproxen, Oseltamivir, A549 Cells, Influenza A virus, Drug Design, Drug Resistance, Viral, Influenza, Human, Animals, Humans, Female
Abstract

International audience; The nucleoprotein (NP) of influenza A virus (IAV) required for IAV replication is a promising target for new antivirals. We previously identified by in silico screening naproxen being a dual inhibitor of NP and cyclooxygenase COX2, thus combining antiviral and anti-inflammatory effects. However, the recently shown strong COX2 antiviral potential makes COX2 inhibition undesirable. Here we designed and synthesized two new series of naproxen analogues called derivatives 2, 3, and 4 targeting highly conserved residues of the RNA binding groove, stabilizing NP monomer without inhibiting COX2. Derivative 2 presented improved antiviral effects in infected cells compared to that of naproxen and afforded a total protection of mice against a lethal viral challenge. Derivative 4 also protected infected cells challenged with circulating 2009-pandemic and oseltamivir-resistant H1N1 virus. This improved antiviral effect likely results from derivatives 2 and 4 inhibiting NP-RNA and NP-polymerase acidic subunit PA N-terminal interactions.

Published
2018

6. Protease-activated receptor 1 inhibition protects mice against thrombin-dependent respiratory syncytial virus and human metapneumovirus infections

Author

Lê, Vuong Ba, Riteau, Beatrice, Alessi, Marie-Christine, Couture, Christian, Jandrot-Perrus, Martine, Rhéaume, Chantal, Hamelin, Marie-Ève, Boivin, Guy, Nutrition, obésité et risque thrombotique (NORT), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fibrinolyse et Pathologie Vasculaire, Université de la Méditerranée - Aix-Marseille 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Hémostase, bio-ingénierie et remodelage cardiovasculaires (LBPC), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Galilée, Centre de Recherche et de Développement en Horticulture (CRDH), and Agriculture et Agroalimentaire Canada

Subjects
[SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience

Published
2018

7. Rôle des plaquettes au cours de l’infection pulmonaire

Author

Riteau, Beatrice, Nutrition, obésité et risque thrombotique (NORT), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), ProdInra, Archive Ouverte, Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Société de Réanimation de Langue Française (SRLF). FRA.

Subjects
thrombocyte, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, grippe, plaquette, infection pulmonaire, hémostase, human influenza, virus, influenza, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, blood coagulation
Abstract

Rôle des plaquettes au cours de l’infection pulmonaire. Seminaire de recherche transactionnelle

Published
2016

12. Rôle des plaquettes au cours des infections grippales

Author

Riteau, Beatrice, ProdInra, Archive Ouverte, Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Club Francais des mégacaryocytes et des plaquettes. FRA., and Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
thrombocyte, grippe, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, infection virale, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Rôle des plaquettes au cours des infections grippales. 4. rencontre du club Francais des mégacaryocytes et des plaquettes

Published
2016

13. The good and bad side of cytokines during influenza virus infections: involvement of homestasis

Author

Riteau, Beatrice, Nutrition, obésité et risque thrombotique (NORT), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plovdiv University 'Paisii Hiledarski'. BGR., Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and ProdInra, Archive Ouverte

Subjects
[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, grippe, viruses, education, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, cytokine, virus, influenza, influenza viruses, cytokines, infection, virus grippal
Abstract

virus, grippe, cytokines; The good and bad side of cytokines during influenza virus infections: involvement of homestasis. Meeting international relationships Plovdiv

Published
2015

14. The good and bad side of cytokines during influenza virus infections: involvement of hemostasis activation

Author

Riteau, Beatrice, Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Flanders Institute for Biotechnology (VIB). Ghent, BEL., Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and ProdInra, Archive Ouverte

Subjects
[SDV] Life Sciences [q-bio], grippe, [SDV]Life Sciences [q-bio], physiologie sanguine, hemostasis, cytokine, hémostase, human influenza, virus, influenza viruses, influenza, blood coagulation, virus grippal
Abstract

The good and bad side of cytokines during influenza virus infections: involvement of hemostasis activation. Emerging Cytokine Networks

Published
2015

15. Influenza, récepteur Par1 et coagulation

Author

Riteau, Beatrice, ProdInra, Archive Ouverte, Nutrition, obésité et risque thrombotique (NORT), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Société Française d'Hématologie (SFH). FRA. Société Française d'Hématologie (SFH), FRA., and Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, thrombocyte, receiver, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, hemostase, human influenza, virus, influenza, récepteur, PAR1
Abstract

Influenza, récepteur Par1 et coagulation. Congrès 2015 de la Société Française d'Hématologie

Published
2015

16. Platelet activation and aggregation promote lung inflammation and influenza virus pathogenesis.

Author

Luxembourg Centre for Systems Biomedicine (LCSB): Medical Translational Research (J. Schneider Group) [research center], Le, Vuong Ba, Schneider, Jochen, Boergeling, Yvonne, Berri, Fatma, Ducatez, Mariette, Guerin, Jean-Luc, Adrian, Iris, Errazuriz-Cerda, Elisabeth, Frasquilho, Sonia, Antunes, Laurent, Lina, Bruno, Bordet, Jean-Claude, Jandrot-Perrus, Martine, Ludwig, Stephan, Riteau, Beatrice, Luxembourg Centre for Systems Biomedicine (LCSB): Medical Translational Research (J. Schneider Group) [research center], Le, Vuong Ba, Schneider, Jochen, Boergeling, Yvonne, Berri, Fatma, Ducatez, Mariette, Guerin, Jean-Luc, Adrian, Iris, Errazuriz-Cerda, Elisabeth, Frasquilho, Sonia, Antunes, Laurent, Lina, Bruno, Bordet, Jean-Claude, Jandrot-Perrus, Martine, Ludwig, Stephan, and Riteau, Beatrice

Abstract

RATIONALE: The hallmark of severe influenza virus infection is excessive inflammation of the lungs. Platelets are activated during influenza, but their role in influenza virus pathogenesis and inflammatory responses is unknown. OBJECTIVES: To determine the role of platelets during influenza A virus infections and propose new therapeutics against influenza. METHODS: We used targeted gene deletion approaches and pharmacologic interventions to investigate the role of platelets during influenza virus infection in mice. MEASUREMENTS AND MAIN RESULTS: Lungs of infected mice were massively infiltrated by aggregates of activated platelets. Platelet activation promoted influenza A virus pathogenesis. Activating protease-activated receptor 4, a platelet receptor for thrombin that is crucial for platelet activation, exacerbated influenza-induced acute lung injury and death. In contrast, deficiency in the major platelet receptor glycoprotein IIIa protected mice from death caused by influenza viruses, and treating the mice with a specific glycoprotein IIb/IIIa antagonist, eptifibatide, had the same effect. Interestingly, mice treated with other antiplatelet compounds (antagonists of protease-activated receptor 4, MRS 2179, and clopidogrel) were also protected from severe lung injury and lethal infections induced by several influenza strains. CONCLUSIONS: The intricate relationship between hemostasis and inflammation has major consequences in influenza virus pathogenesis, and antiplatelet drugs might be explored to develop new antiinflammatory treatment against influenza virus infections.

Published
2015

17. Role of hemostasis during influenza virus infections

Author

Riteau, Beatrice, Département Santé Animale (DEPT SA), Institut National de la Recherche Agronomique (INRA), Virpath-Grippe, de l'émergence au contrôle -- Virpath-Influenza, from emergence to control (Virpath), 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), ANR-13-BSV3-0011, ProdInra, Archive Ouverte, German research Platform for Zoonoses. DEU. Federal Ministry of Education and Research (BMBF), DEU., 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), 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)

Subjects
[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, grippe, viruses, health care facilities, manpower, and services, education, virus diseases, hémostase, human influenza, virus, blood coagulation, virus grippal, infection virale, physiologie sanguine, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, hemostasis, influenza viruses, influenza, health care economics and organizations
Abstract

Role of hemostasis during influenza virus infections. Internal FluResearchNet Meeting 2013

Published
2013

18. Overview on the Role of Immunomodulation, Cellular Factors, and Proteases during influenza virus infections

Author

Riteau, Beatrice, Département Santé Animale (DEPT SA), Institut National de la Recherche Agronomique (INRA), Virpath-Grippe, de l'émergence au contrôle -- Virpath-Influenza, from emergence to control (Virpath), 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), International Society for Influenza and other Respiratory Virus Diseases (ISIRV). INT., ProdInra, Archive Ouverte, 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), 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)

Subjects
[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, grippe, facteur de croissance cellulaire, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, virus diseases, human influenza, protéase, virus, activité immunomodulatrice, influenza viruses, influenza, virus grippal
Abstract

Overview on the Role of Immunomodulation, Cellular Factors, and Proteases during influenza virus infections. Options for the control of influenza 8.

Published
2013

19. HLA-G1 and HLA-G5 active dimers are present in malignant cells and effusions: The influence of the tumor microenvironment

Author

Zilberman, Sonia, Schenowitz, Chantal, Agaugué, Sophie, Benoît, Favier, Riteau, Beatrice, Rouzier, Roman, Carosella, Edgardo D., Rouas-Freiss, Nathalie, and Menier, Catherine

Subjects
tumeur, cancer, dimers, hal-g, malignant effusions, tumor microenvironment, environnement, Cancer
Abstract

Dimers of the nonclassical HLA-G class I molecule have recently been shown to be active structures that mediate inhibition of NK-cell cytotoxic activity through interaction with the immunoglobulin-like transcript (ILT)-2 inhibitory receptor. However, this has only been proven in trophoblasts and HLA-G transfectants. Here, we document for the first time the existence of HLA-G dimers in cancer. Indeed, we identified both surface and soluble HLA-G dimers in tumor cells and malignant ascites respectively. Interestingly, factors from the tumor microenvironment, such as interferons, enhanced the formation of HLA-G dimers and increased the protection of tumors from NK cell-mediated lysis. These data emphasize the impact of HLA-G conformation on its efficiency at inhibitingthe antitumor response and thus favoring tumor progression. In view of these results, the effect of the tumor microenvironment on upregulation of HLA-G function deserves particular attention when designing cancer immunotherapy protocols.

Published
2012

20. Protective role of protease-activated-receptor 2 against influenza viruses occurs through an ERK independent pathway: implication for new influenza therapy

Author

Foucault, Marie-Laure, Moules, Vincent, Ferraris, Olivier, Lina, Bruno, Rosa-Calatrava, Manuel, Riteau, Beatrice, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Département Santé Animale (DEPT SA), Institut National de la Recherche Agronomique (INRA), and ProdInra, Migration

Subjects
[SDV] Life Sciences [q-bio], protease-activated-receptor, PLASMINOGEN, [SDV]Life Sciences [q-bio], HLA-G, REPLICATION, INHIBITION, PROTEOLYTIC ACTIVATION, SIGNALING PATHWAY, new therapeutics, Influenza
Abstract

International audience; To date there is an urgent need to develop new antivirals against influenza. Most of the molecules reported target influenza proteins that acquire rapid mutations of resistance. The development of new molecules that have a broad antiviral activity and are not subjected to influenza mutation is of particular interest. Our laboratory and others recently showed that proteases can participate to the innate immune response in the airways through the activation of a family of receptors called PAR. In particular, through the release of interferon, PAR2 agonists curbed viral replication significantly in infected cells. In this study, since ERK activation is crucial for virus replication, we investigated whether PAR2 could inhibit virus replication through inhibition of the ERK pathway. Results showed that while influenza A infection alone or PAR2 stimulation alone induced ERK activation, PAR2 stimulation does not inhibit ERK activation in influenza infected cells. Thus, PAR2 agonists may be a potential new drug against influenza viruses that could be used in combination with other anti flu therapy such as the inhibition of the ERK pathway.

Published
2011

21. Un point sur la pathogénicité des virus influenza: rôle des protéases et de la molécule immunosuppressive HLA-G

Author

Le Bouder, Fanny, Mandouri, Yassmina, Menier, Catherine, Lejal, Nathalie, Rouas-Freiss, Nathalie, Riteau, Beatrice, Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut National de la Recherche Agronomique (INRA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and ProdInra, Migration

Subjects
[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
Abstract

National audience; La grippe est une maladie infectieuse, causée par les virus influenza, qui se manifeste par la survenue de grandes pandémies entrecoupées d'épidémies saisonnières. Ces infections récurrentes mettent en évidence la menace permanente causée par ces virus. Face à l'émergence récente de nouvelles souches pandémiques (H1N1 2009) et potentiellement pandémiques (H5N1 aviaire) et de leur diffusion dans le reste du monde, l'objectif de cette revue est d'apporter de nouvelles informations sur les mécanismes de pathogénicité des virus influenza A (IAV). La présence dans les sites infectieux de protéases est un des facteurs majeurs contrôlant le tropisme et l'infectiosité des IAV. Au-delà des effets protéolytiques directs sur les protéines virales, les protéases peuvent également agir sur la cellule hôte via l'activation de récepteurs à sept domaines transmembranaires, dénommés protease activated receptors (PARs). Dans un premier temps, cette revue fait le point sur le rôle des protéases et de leurs récepteurs (annexine II et PAR-2) dans la réplication des IAV. Dans un second temps, la revue fait état des travaux récents menés sur la caractérisation de la molécule non classique du complexe majeur d'histocompatibilité (HLA-G) dont l'expression permettrait de contrôler la réponse immunitaire de l'hôte durant l'infection.

Published
2010

22. Protective role for Protease-Activated-Receptor-2 against Influenza virus Pathogenesis via an Interferon-Y dependent pathway

Author

Khoufache, Khaled, LeBouder, F, Morello, Eric, Laurent, Fabrice, Riffault, Sabine, Andrade-Gordon, P, Boullier, Séverine, Vergnolle, Nathalie, Riteau, Beatrice, ProdInra, Migration, Inconnu, Infectiologie Animale et Santé Publique (UR IASP), Institut National de la Recherche Agronomique (INRA), Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Département Santé Animale (DEPT SA), Johnson and Johnson Paharmaceutical Research and Development, Partenaires INRAE, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and University of Calgary

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

National audience

Published
2009

23. Modulation of the influenza virus infection by host proteases and antiproteases

Author

Riteau, Beatrice, Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut National de la Recherche Agronomique (INRA), and ProdInra, Migration

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

National audience

Published
2008

25. Modulation of protease activated receptor 1 influences human metapneumovirus disease severity in a mouse model.

Author

Aerts, Laetitia, Hamelin, Marie-Eve, Rhéaume, Chantal, Lavigne, Sophie, Couture, Christian, Kim, Woojin, Susan-Resiga, Delia, Prat, Annik, Seidah, Nabil G, Vergnolle, Nathalie, Riteau, Beatrice, Boivin, Guy, Aerts, Laetitia, Hamelin, Marie-Eve, Rhéaume, Chantal, Lavigne, Sophie, Couture, Christian, Kim, Woojin, Susan-Resiga, Delia, Prat, Annik, Seidah, Nabil G, Vergnolle, Nathalie, Riteau, Beatrice, and Boivin, Guy

Abstract

Human metapneumovirus (hMPV) infection causes acute respiratory tract infections (RTI) which can result in hospitalization of both children and adults. To date, no antiviral or vaccine is available for this common viral infection. Immunomodulators could represent an interesting strategy for the treatment of severe viral infection. Recently, the role of protease-activated receptors (PAR) in inflammation, coagulation and infection processes has been of growing interest. Herein, the effects of a PAR1 agonist and a PAR1 antagonist on hMPV infection were investigated in BALB/c mice. Intranasal administration of the PAR1 agonist resulted in increased weight loss and mortality of infected mice. Conversely, the PAR1 antagonist was beneficial to hMPV infection by decreasing weight loss and clinical signs and by significantly reducing pulmonary inflammation, pro-inflammatory cytokine levels (including IL-6, KC and MCP-1) and recruitment of immune cells to the lungs. In addition, a significant reduction in pulmonary viral titers was also observed in the lungs of PAR1 antagonist-treated mice. Despite no apparent direct effect on virus replication during in vitro experiments, an important role for PAR1 in the regulation of furin expression in the lungs was shown for the first time. Further experiments indicated that the hMPV fusion protein can be cleaved by furin thus suggesting that PAR1 could have an effect on viral infectivity in addition to its immunomodulatory properties. Thus, inhibition of PAR1 by selected antagonists could represent an interesting strategy for decreasing the severity of paramyxovirus infections., info:eu-repo/semantics/published

Published
2013

26. Modulation of Protease Activated Receptor 1 Influences Human Metapneumovirus Disease Severity in a Mouse Model

Author

Aerts, Laetitia, primary, Hamelin, Marie-Ève, additional, Rhéaume, Chantal, additional, Lavigne, Sophie, additional, Couture, Christian, additional, Kim, WooJin, additional, Susan-Resiga, Delia, additional, Prat, Annik, additional, Seidah, Nabil G., additional, Vergnolle, Nathalie, additional, Riteau, Beatrice, additional, and Boivin, Guy, additional

Published
2013
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27. The influenza fingerprints: NS1 and M1 proteins contribute to specific host cell ultrastructure signatures upon infection by different influenza A viruses

Author

Terrier, Olivier, primary, Moules, Vincent, additional, Carron, Coralie, additional, Cartet, Gaëlle, additional, Frobert, Emilie, additional, Yver, Matthieu, additional, Traversier, Aurelien, additional, Wolff, Thorsten, additional, Riteau, Beatrice, additional, Naffakh, Nadia, additional, Lina, Bruno, additional, Diaz, Jean-Jacques, additional, and Rosa-Calatrava, Manuel, additional

Published
2012
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28. Importance of viral genomic composition in modulating glycoprotein content on the surface of influenza virus particles

Author

Moulès, Vincent, primary, Terrier, Olivier, additional, Yver, Matthieu, additional, Riteau, Beatrice, additional, Moriscot, Christine, additional, Ferraris, Olivier, additional, Julien, Thomas, additional, Giudice, Emmanuel, additional, Rolland, Jean-Paul, additional, Erny, Alexandra, additional, Bouscambert-Duchamp, Maude, additional, Frobert, Emilie, additional, Rosa-Calatrava, Manuel, additional, Pu Lin, Yi, additional, Hay, Alan, additional, Thomas, Daniel, additional, Schoehn, Guy, additional, and Lina, Bruno, additional

Published
2011
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29. Plasmacytoid Dendritic Cells Migrate in Afferent Skin Lymph

Author

Pascale, Florentia, primary, Contreras, Vanessa, additional, Bonneau, Michel, additional, Courbet, Alexandre, additional, Chilmonczyk, Stefan, additional, Bevilacqua, Claudia, additional, Eparaud, Mathieu, additional, Niborski, Violeta, additional, Riffault, Sabine, additional, Balazuc, Anne-Marie, additional, Foulon, Eliane, additional, Guzylack-Piriou, Laurence, additional, Riteau, Beatrice, additional, Hope, Jayne, additional, Bertho, Nicolas, additional, Charley, Bernard, additional, and Schwartz-Cornil, Isabelle, additional

Published
2008
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32. Antagonists of PAR1: towards a new antiviral strategy against Flu

Author

Béatrice Riteau, Bruno Lina, Riteau, Beatrice, Virologie et pathologie humaine (VirPath), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Département Santé Animale (DEPT SA), and Institut National de la Recherche Agronomique (INRA)

Subjects
0303 health sciences, grippe, business.industry, maladie contagieuse, protéase, General Medicine, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Santé publique et épidémiologie, 0302 clinical medicine, antagoniste, réplication virale, vaccination humaine, inflammation, virus influenza, Medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 030215 immunology
Abstract

National audience

Published
2013

33. Vav1 phosphorylation is induced by beta2 integrin engagement on natural killer cells upstream of actin cytoskeleton and lipid raft reorganization.

Author

Riteau B, Barber DF, and Long EO

Subjects
Actins metabolism, Animals, Cell Line, Humans, Intercellular Adhesion Molecule-1 metabolism, Phosphorylation, Protein Binding, Proto-Oncogene Proteins c-vav, Receptors, Immunologic genetics, Receptors, Immunologic metabolism, Tyrosine metabolism, CD18 Antigens metabolism, Cell Cycle Proteins, Cytoskeleton metabolism, Killer Cells, Natural metabolism, Lymphocyte Function-Associated Antigen-1 metabolism, Membrane Microdomains metabolism, Proto-Oncogene Proteins metabolism
Abstract

The guanine nucleotide exchange factor Vav1 regulates actin polymerization and contributes to cytotoxicity by natural killer (NK) cells. An open question is how Vav1 becomes activated and what receptor can signal upstream of actin cytoskeleton rearrangement upon NK cell contact with target cells. Using transfected insect cells that express ligands of human NK cell receptors, we show that engagement of the beta2 integrin LFA-1 on NK cells by intercellular adhesion molecule (ICAM)-1 led to a tyrosine phosphorylation of Vav1 that was not sensitive to cholesterol depletion and to inhibition of actin polymerization. Vav1 phosphorylation was blocked by an inhibitor of Src-family kinases, and correlated with activation of its downstream effector PAK. Binding of activation receptor 2B4 to its ligand CD48 was not sufficient for Vav1 phosphorylation. However, coengagement of 2B4 with LFA-1 resulted in an enhancement of Vav1 phosphorylation that was sensitive to cholesterol depletion and to inhibition of actin polymerization. Vav1 was recruited to a detergent-resistant membrane (DRM) fraction only when 2B4 and LFA-1 were coengaged, but not after LFA-1 engagement. Therefore, binding of LFA-1 to ICAM-1 on target cells may initiate an early signaling cascade in NK cells through activation of Vav1, leading to cytoskeleton reorganization and amplification of signals from other activation receptors.

Published
2003
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