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29 results on '"MESH: Cytomegalovirus Infections"'

1. Repertoire characterization and validation of gB-specific human IgGs directly cloned from humanized mice vaccinated with dendritic cells and protected against HCMV

Author

Torsten Witte, Martin Messerle, Andreas Schneider, Johannes Koenig, Sebastian J. Theobald, Michael Mach, Matthias Ballmaier, Simon Danisch, Henning Olbrich, Renata Stripecke, Agnes Bonifacius, Lutz Gieselmann, Constanca Figueiredo, Michael Meyer-Hermann, Meryem S. Ercanoglu, Constantin von Kaisenberg, Frank Klawonn, Britta Eiz-Vesper, Florian Klein, Marija Backovic, Christoph Kreer, Sahamoddin Khailaie, Valery Volk, Hannover Medical School [Hannover] (MHH), German Center for Infection Research - partner site Hannover-Braunschweig (DZIF), University of Cologne, University Hospital of Cologne [Cologne], Helmholtz Centre for Infection Research (HZI), Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), German Center for Infection Research - Partner Site Bonn-Cologne (DZIF), Ostfalia University of Applied Sciences, Technische Universität Braunschweig = Technical University of Braunschweig [Braunschweig], R.S./S.T./V.V./H.O. Hannover: This work was financed by grants of the German Center for Infections Research (DZIF-TTU07.803 and DZIF-TTU07.805 to R.S.), by a research collaboration grant of 'The Jackson Laboratory' and by the German Research Council (DFG/SFB738 Project A6 to R.S. and MM, DFG/REBIRTH Unit 6.4 to R.S.). S.T. received a RegSci Ph.D. fellowship, H.O. received a DZIF-Strucmed fellowship and V.V. received a DAAD/ZIB Ph.D. fellowship. F.K./C.K./ Univ. Cologne: This work was funded by grants from the German Center for Infection Research (DZIF, F.K.), the German Research Foundation (CRC 1279, F.K., CRC 1310, C.K. and F.K., Heisenberg-Program KL2389/2-1, F.K.) and the European Research Council (ERC-StG639961, F.K.). M.M.-H./ S.K./ Braunschweig: S.K. was supported by the German Federal Ministry of Education and Research (BMBF) for the eMED project SYSIMIT and by the Helmholtz-Gemeinschaft, Zukunftsthema 'Immunology and Inflammation' (ZT-0027)., European Project: 639961,H2020,ERC-2014-STG,HIV1ABTHERAPY(2016), BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany, HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany., and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)

Subjects
B Cells, Pathology and Laboratory Medicine, Antibodies, Viral, Biochemistry, MESH: Antibodies, Monoclonal, MESH: Antibodies, Neutralizing, Mice, Animal Cells, Cytotoxic T cell, MESH: Animals, Biology (General), Enzyme-Linked Immunoassays, Immune Response, MESH: Immunoglobulin G, 0303 health sciences, 030302 biochemistry & molecular biology, Antibodies, Monoclonal, 3. Good health, Medical Microbiology, Viral Pathogens, MESH: Immunization, Passive, Antibody, Blood cells, QH301-705.5, T cell, Immunology, Cytotoxic T cells, Microbiology, 03 medical and health sciences, Antigen, Genetics, Humans, Antibody-Producing Cells, Immunoassays, Molecular Biology, Microbial Pathogens, MESH: Humans, Organisms, Immunization, Passive, Proteins, Correction, MESH: Cytomegalovirus Infections, Dendritic Cells, biochemical phenomena, metabolism, and nutrition, medicine.disease, Virology, Antibodies, Neutralizing, Animal Studies, Parasitology, Immunologic diseases. Allergy, MESH: Disease Models, Animal, MESH: Antibodies, Viral, Human cytomegalovirus, Physiology, [SDV]Life Sciences [q-bio], Cytomegalovirus, White Blood Cells, Cytomegalovirus Vaccines, Medizinische Fakultät, Immune Physiology, Cellular types, Medicine and Health Sciences, Antigens, Viral, Immune System Proteins, biology, MESH: Dendritic Cells, T Cells, Immune cells, Animal Models, medicine.anatomical_structure, Experimental Organism Systems, Viruses, Cytomegalovirus Infections, Human Cytomegalovirus, Pathogens, MESH: Antigens, Viral, Research Article, MESH: Cytomegalovirus, Cell biology, Herpesviruses, Somatic hypermutation, Mouse Models, Research and Analysis Methods, Antibodies, Immune system, Model Organisms, MESH: Cytomegalovirus Vaccines, medicine, Animals, ddc:610, MESH: Mice, 030304 developmental biology, Biology and life sciences, RC581-607, Disease Models, Animal, Immunization, Immunoglobulin G, biology.protein, Immunologic Techniques, DNA viruses
Abstract

Human cytomegalovirus (HCMV) causes serious complications to immune compromised hosts. Dendritic cells (iDCgB) expressing granulocyte-macrophage colony-stimulating factor, interferon-alpha and HCMV-gB were developed to promote de novo antiviral adaptive responses. Mice reconstituted with a human immune system (HIS) were immunized with iDCgB and challenged with HCMV, resulting into 93% protection. Immunization stimulated the expansion of functional effector memory CD8+ and CD4+ T cells recognizing gB. Machine learning analyses confirmed bone marrow T/CD4+, liver B/IgA+ and spleen B/IgG+ cells as predictive biomarkers of immunization (≈87% accuracy). CD8+ and CD4+ T cell responses against gB were validated. Splenic gB-binding IgM-/IgG+ B cells were sorted and analyzed at a single cell level. iDCgB immunizations elicited human-like IgG responses with a broad usage of various IgG heavy chain V gene segments harboring variable levels of somatic hypermutation. From this search, two gB-binding human monoclonal IgGs were generated that neutralized HCMV infection in vitro. Passive immunization with these antibodies provided proof-of-concept evidence of protection against HCMV infection. This HIS/HCMV in vivo model system supported the validation of novel active and passive immune therapies for future clinical translation., Author summary Human cytomegalovirus (HCMV) is a ubiquitous pathogen. As long as the immune system is functional, T and B cells can control HCMV. Yet, for patients who have debilitated immune functions, HCMV infections and reactivations cause major complications. Vaccines or antibodies to prevent or treat HCMV are not yet approved. Novel animal models for testing new immunization approaches are emerging and are important tools to identify biomedical products with a reasonable chance to work in patients. Here, we used a model based on mice transplanted with human immune cells and infected with a traceable HCMV. We tested a cell vaccine (iDCgB) carrying gB, a potent HCMV antigen. The model showed that iDCgB halted the HCMV infection in more than 90% of the mice. We found that antibodies were key players mediating protection. Using state-of-the-art methods, we were able to use the sequences of the human antibodies generated in the mice to construct and produce monoclonal antibodies in the laboratory. Proof-of-concept experiments indicated that administration of these monoclonal antibodies into mice protected them against HCMV infection. In summary, this humanized mouse model was useful to test a vaccine and to generate and test novel antibodies that can be further developed for human use.

Published
2019
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2. Étude des facteurs prédictifs de séquelles à 2 ans en lien avec une infection congénitale à Cytomégalovirus

Author

Petermann, Lucile, Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), and Jean-François Magny

Subjects
MESH: Cytomegalovirus, MESH: Immunologic Deficiency Syndromes, Dépistage sérologique systématique, MESH: Maternal Serum Screening Tests, Handicap, Symptomatic, Trouble neuro-développemental, MESH: Prognosis, Hearing impairment, Congenital infection, Infection congénitale, MESH: Risk Factors, Pronostic, MESH: Therapeutics, Traitement, MESH: Hearing Loss, MESH: Neurodevelopmental Disorders, Facteurs de risques, MESH: Cytomegalovirus Infections, MESH: Disabled Persons, Cytomégalovirus, Déficience, Déficience auditive, Impairment, Symptomatique, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Objectives: cytomegalovirus (CMV) is the leading cause of congenital infection in the world with a major risk of sequelae including neurological and auditory. The aim of the study is to identify what are the prognostic factors for defining neonates at risk of developing sequelae at 2 years related to congenital CMV infection. Design of the study: monocentric retrospective observational study including 220 patients born between January 2001 and October 2015 with congenital CMV infection. We studied various pre- and postnatal factors and their impact on the outcome at 2 years of age for children with congenital CMV infection. Results: the presence of at least one postnatal abnormality (clinical examination or additional investigations) was a risk factor for developing sequelae at 2 years (p = 0.037). Neonates with maternal seroconversion in the first trimester were more likely to develop sequelae at 2 years (p

Published
2018

3. Guillain-Barré syndrome and cytomegalovirus infection during pregnancy

Author

Olivier Casez, Monique Baccard-Longère, Julien Lupo, Dominique Jean, Jean Boutonnat, Raphaële Germi, Gérard Besson, Pascale Hoffmann, Patrice Morand, Carole Schwebel, Alain Rougé, Université Grenoble Alpes - UFR Pharmacie (UGA UFRP), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), 'Personal Protection Against Vectors' working group (PPAV), PPAV working group, Laboratoire de virologie, Centre Hospitalo-Universitaire de Grenoble, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Pôle Psychiatrie et Neurologie [Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Université de Lorraine (UL), CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Service de Réanimation Médicale [Grenoble], CHU Grenoble-Hôpital Michallon, Biologie du Cancer et de l'Infection (BCI ), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG)

Subjects
Cytomegalovirus, 0302 clinical medicine, MESH: Pregnancy, Pregnancy, Congenital infection, Medicine, 030212 general & internal medicine, MESH: Immunoglobulins, Intravenous, reproductive and urinary physiology, MESH: Treatment Outcome, biology, Fetal death, Guillain-Barre syndrome, Immunoglobulins, Intravenous, virus diseases, Guillain-Barré syndrome, 3. Good health, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Treatment Outcome, Infectious Diseases, In utero, MESH: Pregnancy Complications, Cytomegalovirus Infections, Female, Antibody, Adult, MESH: Antiviral Agents, Congenital cytomegalovirus infection, Immunoglobulins, Guillain-Barre Syndrome, Antiviral Agents, 03 medical and health sciences, Virology, Humans, Fetal Death, MESH: Guillain-Barre Syndrome, Fetus, MESH: Humans, business.industry, MESH: Adult, MESH: Cytomegalovirus Infections, medicine.disease, Pregnancy Complications, Cytomegalovirus infection, Immunology, biology.protein, bacteria, MESH: Fetal Death, business, MESH: Female, 030217 neurology & neurosurgery
Abstract

International audience; Guillain-Barré syndrome (GBS) is an immune-mediated disorder which can be triggered by cytomegalovirus (CMV) infection. GBS following CMV primary infection is a rare event during pregnancy, which raises the question of maternal and fetal management. We describe an unusual case of GBS after CMV primary infection in a pregnant woman. The mother was successfully treated with standard immunoglobulins but in utero fetal death caused by CMV congenital infection unfortunately occurred. Similar cases have rarely been reported in the literature.

Published
2016
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4. Aminobisphosphonates Synergize with Human Cytomegalovirus To Activate the Antiviral Activity of Vγ9Vδ2 Cells

Author

Suzanne Peyrottes, Eric Champagne, Charline Daguzan, Christian Davrinche, Morgane Moulin, Hanna Kulyk-Barbier, Centre de Physiopathologie Toulouse Purpan (ex IFR 30 et IFR 150) (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM), Université Montpellier 2 - Sciences et Techniques (UM2), Ecole Nationale Supérieure de Chimie de Montpellier, and Grant Number : Fondation pour la Recherche Medicale Grant [DCM20121225761], Comité d'éthique de l'Inserm (CEI), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), 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), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)

Subjects
Cytotoxicity, Immunologic, 0301 basic medicine, Human cytomegalovirus, lymphocytes, bisphosphonate, [SDV]Life Sciences [q-bio], Isopentenyl pyrophosphate, Cytomegalovirus, hiv-infection, MESH: T-Lymphocyte Subsets, Lymphocyte Activation, Virus Replication, stimulation, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, chemistry.chemical_compound, zoledronic acid, T-Lymphocyte Subsets, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Immunology and Allergy, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, MESH: Cytokines, Diphosphonates, MESH: Dendritic Cells, Receptors, Antigen, T-Cell, gamma-delta, tumor-cells, MESH: Mevalonic Acid, inhibition, 3. Good health, MESH: Leukocytes, Mononuclear, medicine.anatomical_structure, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Cytomegalovirus Infections, Host-Pathogen Interactions, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, Tumor necrosis factor alpha, receptor-gamma, delta t-cells, MESH: Cells, Cultured, MESH: Cytomegalovirus, replication, MESH: Diphosphonates, T cell, Immunology, Mevalonic Acid, Biology, Cell Line, 03 medical and health sciences, Antigen, MESH: Receptors, Antigen, T-Cell, gamma-delta, medicine, Humans, MESH: Cytotoxicity, Immunologic, MESH: Lymphocyte Activation, MESH: Humans, T-cell receptor, MESH: Virus Replication, MESH: Host-Pathogen Interactions, Lymphokine, Dendritic Cells, MESH: Cytomegalovirus Infections, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.disease, Virology, MESH: Cell Line, 030104 developmental biology, chemistry, Cell culture, Leukocytes, Mononuclear, Cancer research, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Human V gamma 9V delta 2 T cells are activated through their TCR by neighboring cells producing phosphoantigens. Zoledronate (ZOL) treatment induces intracellular accumulation of the phosphoantigens isopentenyl pyrophosphate and ApppI. Few attempts have been made to use immunomanipulation of V gamma 9V delta 2 lymphocytes in chronic viral infections. Although V gamma 9V delta 2 T cells seem to ignore human CMV (HCMV)-infected cells, we examined whether they can sense HCMV when a TCR stimulus is provided with ZOL. Fibroblasts treated with ZOL activate V gamma 9V delta 2 T cells to produce IFN-gamma but not TNF. Following the same treatment, HCMV-infected fibroblasts stimulate TNF secretion and an increased production of IFN-g, indicating that V gamma 9V delta 2 cells can sense HCMV infection. Increased lymphokine production was observed with most clinical isolates and laboratory HCMV strains, HCMV-permissive astrocytoma, or dendritic cells, as well as "naive" and activated V gamma 9V delta 2 cells. Quantification of intracellular isopentenyl pyrophosphate/ApppI following ZOL treatment showed that HCMV infection boosts their accumulation. This was explained by an increased capture of ZOL and by upregulation of HMG-CoA synthase and reductase transcription. Using an experimental setting where infected fibroblasts were cocultured with gamma delta cells in submicromolar concentrations of ZOL, we show that V gamma 9V delta 2 cells suppressed substantially the release of infectious particles while preserving uninfected cells. V gamma 9V delta 2 cytotoxicity was decreased by HCMV infection of targets whereas anti-IFN-gamma and anti-TNF Abs significantly blocked the antiviral effect. Our experiments indicate that cytokines produced by V gamma 9V delta 2 T cells have an antiviral potential in HCMVinfection. This should lead to in vivo studies to explore the possible antiviral effect of immunostimulation with ZOL in this context.

Published
2016
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5. Severe systemic cytomegalovirus infections in patients with steroid-refractory ulcerative colitis treated by an oral microemulsion form of cyclosporine: Report of two cases

Author

Franck Carbonnel, G. Piton, A. C. Dupont-Gossart, Georges Mantion, G. Herbein, G. Viennet, Audrey Weber, Agents pathogènes et inflammation - UFC (EA 4266) (API), Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)

Subjects
Adult, MESH: Emulsions, medicine.medical_specialty, medicine.medical_treatment, MESH: Colitis, Ulcerative, Congenital cytomegalovirus infection, Administration, Oral, Context (language use), medicine.disease_cause, Severity of Illness Index, MESH: Cyclosporine, Gastroenterology, Herpesviridae, 03 medical and health sciences, 0302 clinical medicine, Betaherpesvirinae, MESH: Severity of Illness Index, Internal medicine, medicine, Humans, MESH: Humans, biology, business.industry, MESH: Adult, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Immunosuppression, MESH: Cytomegalovirus Infections, General Medicine, medicine.disease, biology.organism_classification, Ciclosporin, Ulcerative colitis, 3. Good health, Discontinuation, 030220 oncology & carcinogenesis, Cytomegalovirus Infections, MESH: Administration, Oral, Immunology, Cyclosporine, Colitis, Ulcerative, Emulsions, Female, 030211 gastroenterology & hepatology, MESH: Immunosuppressive Agents, business, MESH: Female, Immunosuppressive Agents, medicine.drug
Abstract

International audience; CMV reactivation is frequently observed in acute flares of ulcerative colitis (UC), particularly those which do not respond to intravenous steroids. Several recent series have suggested that, in most cases, CMV reactivation does not lead to severe complications and resolves spontaneously with the UC flare and discontinuation of immunosuppression. In the present paper, we describe two patients with active UC who developed a severe systemic CMV infection during a treatment with an oral microemulsion form of cyclosporine. This is of concern, particularly in a context of increasing use of immunosuppressive drugs in UC. We propose a prophylactic and curative approach to decrease morbidity related to CMV infection in active UC.

Published
2008
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6. Urinary cytotoxic molecular markers for a noninvasive diagnosis in acute renal transplant rejection*

Author

Sophie Felix, Gérard Rifle, Christophe Ferrand, Jean-Michel Rebibou, Philippe Saas, Jean-Marc Chalopin, Pierre Tiberghien, Maria Yannaraki, Patrick Hervé, Anne Duperrier, Didier Ducloux, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service d'urologie, andrologie et transplantation rénale, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, Plateforme de Biomonitoring, Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Service d'Anatomie pathologique [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de néphrologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Saas, Philippe, and Hôpital Saint-Jacques-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)

Subjects
Graft Rejection, Male, Nephrology, Pathology, MESH: Membrane Glycoproteins, 030232 urology & nephrology, MESH: Urinary Tract Infections, 030230 surgery, Gastroenterology, Granzymes, MESH: Kidney Transplantation, Postoperative Complications, 0302 clinical medicine, Chronic allograft nephropathy, MESH: Postoperative Complications, MESH: Reverse Transcriptase Polymerase Chain Reaction, Lymphocytes, MESH: Serine Endopeptidases, Kidney transplantation, Kidney, Membrane Glycoproteins, MESH: Middle Aged, MESH: Pore Forming Cytotoxic Proteins, Reverse Transcriptase Polymerase Chain Reaction, Serine Endopeptidases, MESH: Tumor Necrosis Factors, Middle Aged, MESH: Predictive Value of Tests, 3. Good health, MESH: Reproducibility of Results, medicine.anatomical_structure, Real-time polymerase chain reaction, Acute Disease, Cytomegalovirus Infections, Tumor Necrosis Factors, Urinary Tract Infections, MESH: Acute Disease, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Pore Forming Cytotoxic Proteins, medicine.medical_specialty, Fas Ligand Protein, [SDV.IMM] Life Sciences [q-bio]/Immunology, Urinary system, MESH: Graft Rejection, Sensitivity and Specificity, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, MESH: Transplantation, Homologous, medicine, Humans, Transplantation, Homologous, RNA, Messenger, MESH: RNA, Messenger, MESH: Granzymes, Transplantation, MESH: Humans, Perforin, business.industry, MESH: Biological Markers, Reproducibility of Results, MESH: Cytomegalovirus Infections, medicine.disease, Kidney Transplantation, MESH: Male, MESH: Sensitivity and Specificity, MESH: Fas Ligand Protein, MESH: Perforin, MESH: Lymphocytes, Complication, business, MESH: Female, Biomarkers
Abstract

International audience; Perforin (P), Granzyme B (GB) and Fas-Ligand (FAS-L) are cytotoxic molecules involved in acute rejection (AR) after renal transplantation. A noninvasive diagnostic test to monitor AR and other complications could improve clinical management. We investigated the predictive and diagnostic interest of target mRNA measurements, with a quantitative PCR assay, in AR, as well as in other clinical complications recurrent in kidney transplantation. One hundred and sixty-two urine specimens from 37 allograft recipients were investigated. Clinical settings were AR, urinary tract infection (UTI), cytomegalovirus infection (CMVi) or disease (CMVd), chronic allograft nephropathy (CAN), delayed graft function (DGF) and stable graft course (controls). In the case of AR, mRNA levels of all three molecules were significantly higher than in recipients not showing any clinically evident signs of complication. Indeed, it was observed that expression levels of P, GB and Fas-L mRNA also increase in other clinical situations such as UTI, CMV and DGF. Finally, kinetic studies in three patients with AR revealed that increased P, GB and Fas-L mRNA levels could precede or were concomitant with increased serum creatinin levels. P, GB and Fas-L gene expression in urine specimens were upregulated in AR episodes but also in UTI, CMV infection and DGF. Therefore, this technique would appear to be of limited clinical value as a noninvasive method of diagnosing AR.

Published
2006
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7. The when and wheres of CDC25 phosphatases

Author

Christine Dozier, Bernard Ducommun, Rose Boutros, Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération (LBCMCP), Université Toulouse III - Paul Sabatier (UT3), 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)-Centre de Biologie Intégrative (CBI), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Cell, Cell Cycle Proteins, MESH: Cell Cycle, Quinolones, MESH: Benzoquinones, MESH: Pregnancy, 0302 clinical medicine, MESH: cdc25 Phosphatases, MESH: Risk Factors, Neoplasms, Benzoquinones, MESH: Neoplasms, MESH: Animals, MESH: Incidence, MESH: Naphthoquinones, 0303 health sciences, Transition (genetics), biology, Cell Cycle, MESH: Infant, Newborn, Quinones, 3. Good health, Cell biology, Isoenzymes, medicine.anatomical_structure, 030220 oncology & carcinogenesis, MESH: Isoenzymes, biological phenomena, cell phenomena, and immunity, Gene isoform, CDC25A, Cdc25, DNA damage, MESH: Thiazoles, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Models, Biological, MESH: Quinones, Normal cell, 03 medical and health sciences, MESH: Cell Cycle Proteins, MESH: United States, medicine, Animals, Humans, cdc25 Phosphatases, MESH: Pregnancy Complications, Infectious, 030304 developmental biology, MESH: Quinolones, MESH: Humans, Cdc25 Phosphatases, MESH: Models, Biological, MESH: Cytomegalovirus Infections, Cell Biology, Thiazoles, enzymes and coenzymes (carbohydrates), biology.protein, MESH: Female, Naphthoquinones
Abstract

The CDC25 phosphatases are key regulators of normal cell division and the cell's response to DNA damage. Earlier studies suggested non-overlapping roles for each isoform during a specific cell cycle phase. However, recent data suggest that multiple CDC25 isoforms cooperate to regulate each cell cycle transition. For instance, although CDC25A was initially thought to exclusively regulate the G(1)-S transition, recent data demonstrate a significant role for CDC25A in the G(2)-M transition. Further evidence demonstrates that in addition to the ATM/ATR-CHK pathway, a p38-MAPKAP pathway is also involved in controlling CDC25 activity during G(2)/M checkpoint activation. Together with the fact that CDC25 overexpression is reported in many cancers, these data highlight the significance of developing specific CDC25 inhibitors for cancer therapy.

Published
2006
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8. A Novel Mutation in the Ul54 Gene of Human Cytomegalovirus Isolates that Confers Resistance to Foscarnet

Author

Marie-José Sanson-Le Pors, Françoise Petit, Sophie Alain, Gaël Champier, Marie-Christine Mazeron, Alexandra Ducancelle, Bucek, Ingrid, Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université de Limoges (UNILIM), Biologie moléculaire et cellulaire des microorganismes (EA3175), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7)

Subjects
Foscarnet, Human cytomegalovirus, viruses, Cytomegalovirus, DNA-Directed DNA Polymerase, Drug resistance, Recombinant virus, chemistry.chemical_compound, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: DNA-Directed DNA Polymerase, Pharmacology (medical), Recombination, Genetic, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Microbial Sensitivity Tests, MESH: Drug Resistance, Viral, virus diseases, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Cytomegalovirus Infections, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Recombination, Genetic, MESH: Foscarnet, Cidofovir, medicine.drug, MESH: Antiviral Agents, Ganciclovir, MESH: Cytomegalovirus, MESH: Mutation, Microbial Sensitivity Tests, Biology, Antiviral Agents, Virus, Viral Proteins, Drug Resistance, Viral, medicine, Humans, Pharmacology, MESH: Humans, MESH: Cytomegalovirus Infections, Fibroblasts, biochemical phenomena, metabolism, and nutrition, medicine.disease, MESH: Viral Proteins, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Virology, chemistry, MESH: Fibroblasts, Foscarnet Sodium, Mutation, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract

International audience; Foscarnet is currently licensed for the treatment of human cytomegalovirus (HCMV) infection. Mutations proven to confer resistance to foscarnet have mostly been mapped to regions II, III and VI of the HCMV UL54-encoded DNA polymerase. We previously showed that sequential foscarnet-resistant HCMV isolates recovered from a patient with lymphoma had change N495K in region delta-C of the DNA polymerase. To evaluate the impact of change N495K on HCMV sensitivity to foscarnet, a recombinant HCMV strain carrying the mutation was produced by homologous recombination. The recombinant virus showed a 3.4-fold increase in foscarnet resistance, and remained sensitive to ganciclovir and cidofovir. In addition, the recombinant strain showed a reduction of infectious virus yield compared with its parent strain. Change N495K should be added to the list of mutations conferring resistance to foscarnet and be taken into account in the genotypic diagnosis of antiviral resistance.

Published
2005
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9. Human Cytomegalovirus Binding to DC-SIGN Is Required for Dendritic Cell Infection and Target Cell trans-Infection

Author

Thierry Delaunay, Franck Fieschi, Julie Déchanet-Merville, Fernando Arenzana-Seisdedos, Ali Amara, Franck Halary, Martin Messerle, Corinne Houles, Jean Francois Moreau, Hugues Lortat-Jacob, Génomique, développement et pouvoir pathogène (GD2P), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA), Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Institut de biologie structurale (IBS - UMR 5075), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Pathogénie Virale, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Pathologies infectieuses et cancers : aspects biologiques et thérapeutiques (PICABT), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut Bergonié - CRLCC Bordeaux-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hétérochimie moléculaire et macromoléculaire (HMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Pathogénie Virale - Viral Pathogenesis, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Bergonié [Bordeaux], and UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Human cytomegalovirus, [SDV]Life Sciences [q-bio], Cytomegalovirus, Ligands, Virus Replication, IMMUNOLOGIE, 0302 clinical medicine, Viral Envelope Proteins, MESH: Ligands, Immunology and Allergy, ComputingMilieux_MISCELLANEOUS, MESH: Receptors, Cell Surface, 0303 health sciences, biology, MESH: Dendritic Cells, Cell adhesion molecule, CMV, virus diseases, 3. Good health, DC-SIGN, Infectious Diseases, Cytomegalovirus Infections, MESH: Cell Adhesion Molecules, MESH: Cytomegalovirus, Immunology, Congenital cytomegalovirus infection, Receptors, Cell Surface, Virus, 03 medical and health sciences, Immune system, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Lectins, C-Type, 030304 developmental biology, MESH: Humans, MESH: Virus Replication, Dendritic cell, MESH: Cytomegalovirus Infections, Dendritic Cells, medicine.disease, Virology, Viral replication, MESH: Viral Envelope Proteins, MESH: HeLa Cells, biology.protein, Cell Adhesion Molecules, MESH: Lectins, C-Type, 030215 immunology, HeLa Cells
Abstract

International audience; Cytomegalovirus (CMV) infection is characterized by host immunosuppression and multiorganic involvement. CMV-infected dendritic cells (DC) were recently shown to display reduced immune functions, but their role in virus dissemination is not clear. In this report, we demonstrated that CMV could be captured by DC through binding on DC-SIGN and subsequently transmitted to permissive cells. Moreover, blocking DC-SIGN by specific antibodies inhibited DC infection by primary CMV isolates and expression of DC-SIGN or its homolog DC-SIGNR rendered susceptible cells permissive to CMV infection. We demonstrated that CMV envelope glycoprotein B is a viral ligand for DC-SIGN and DC-SIGNR. These results provide new insights into the molecular interactions contributing to cell infection by CMV and extend DC-SIGN implication in virus propagation.

Published
2002
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10. Infections et grossesse : un danger pour la mère et l'enfant

Author

Charlier, Caroline, Lecuit, Marc, Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service des Maladies infectieuses et tropicales [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre collaborateur de l'OMS Listeria / WHO Collaborating Centre Listeria (CC-OMS / WHO-CC), Institut Pasteur [Paris]-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Biologie des Infections - Biology of Infection, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP]-Institut des Maladies Génétiques Imagine [Paris], and Centre collaborateur de l'OMS Listeria - Biologie des Infections (CCOMS)

Subjects
MESH: Humans, [SDV]Life Sciences [q-bio], MESH: Rubella, MESH: Rubella Syndrome, Congenital, MESH: Vaccination, MESH: Cytomegalovirus Infections, MESH: HIV Infections, MESH: Streptococcus agalactiae, MESH: Male, MESH: HIV-1, MESH: Infectious Disease Transmission, Vertical, MESH: Pregnancy, MESH: Streptococcal Infections, MESH: Listeriosis, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Chickenpox, MESH: Pregnancy Complications, Infectious, MESH: Contraindications, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Chaque année, on dénombre plus de 800 000 grossesses en France. Il n'est pas rare au cours de cette période qu'une femme enceinte soit confrontée à un événement évoquant une infection : fièvre, contage infectieux, découverte d'anomalies sérologiques lors de dépistages systématiques, prescription de traitements antibiotiques, administration d'un vaccin sont autant de situations fréquentes, dont le clinicien doit avoir la maîtrise chez la femme enceinte. Des enjeux multiples Les enjeux d'une infection maternelle sont multiples et souvent chevauchants. Le premier est maternel, car certaines infections sont démontrées plus sévères chez la femme enceinte.

Published
2014
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11. Success and failure of artesunate treatment in five transplant recipients with disease caused by drug-resistant cytomegalovirus

Author

Patrice Morand, Raphaëlle Germi, Paolo Malvezzi, A. Thiebaut, O. Epaulard, Julien Lupo, Sophie Alain, C. Mariette, C. Saint Raymond, J. P. Brion, Unit for Virus Host-Cell Interactions [Grenoble] (UVHCI), Centre National de la Recherche Scientifique (CNRS)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Université Joseph Fourier - Grenoble 1 (UJF), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Service de Bactériologie, Virologie, Hygiène [CHU Limoges], CHU Limoges, Molécules bioactives, conception, isolement et synthèse (MBCIS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Service des Maladies Infectieuses, CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), and Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille

Subjects
Male, Foscarnet, Artesunate, Cytomegalovirus, Drug resistance, chemistry.chemical_compound, MESH: Treatment Outcome, 0303 health sciences, MESH: Middle Aged, MESH: Drug Resistance, Viral, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Hematopoietic Stem Cell Transplantation, virus diseases, MESH: Transplantation, Middle Aged, Viral Load, Artemisinins, 3. Good health, Treatment Outcome, Cytomegalovirus Infections, Female, MESH: Viral Load, medicine.drug, Cidofovir, Ganciclovir, MESH: Antiviral Agents, MESH: Cytomegalovirus, Congenital cytomegalovirus infection, MESH: Organ Transplantation, Antiviral Agents, 03 medical and health sciences, Virology, Drug Resistance, Viral, MESH: Artemisinins, medicine, Humans, MESH: Hematopoietic Stem Cell Transplantation, 030304 developmental biology, Pharmacology, Transplantation, MESH: Humans, 030306 microbiology, business.industry, Organ Transplantation, MESH: Cytomegalovirus Infections, medicine.disease, MESH: Male, Multiple drug resistance, chemistry, Immunology, business, MESH: Female
Abstract

International audience; Cytomegalovirus (CMV) strains resistant to ganciclovir, cidofovir and/or foscarnet were genotypically and phenotypically characterised in two haematopoietic stem cell transplant recipients and three solid-organ transplant recipients with CMV disease. The anti-malaria drug artesunate led to a favourable virological and clinical response in three cases with mild CMV diseases (fever and neutropaenia) but was ineffective in two fatal CMV diseases with lung involvement in spite of a decrease in the CMV DNA load in blood and bronchoalveolar fluid.

Published
2014

12. Human herpes virus co-infection is associated with mortality in HIV-negative patients with Pneumocystis jirovecii pneumonia

Author

Pierre Fillatre, H. Leroy, Y. Le Tulzo, Stéphane Jouneau, Pierre Tattevin, Matthieu Revest, Florence Robert-Gangneux, Sylviane Chevrier, Sophie Minjolle, Arnaud Gacouin, Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes], CHU Pontchaillou [Rennes], Service de Parasitologie-Mycologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Unité de maladies infectieuses, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)-Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes], CHU Pontchaillou [Rennes]-CHU Pontchaillou [Rennes], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Contaminants Chimiques, immunité et Inflammation, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Laboratoire de Virologie [Rennes] = Virology [Rennes], Fonction structure et inactivation d'ARN bactérien, CHU Pontchaillou [Rennes]-CHU Pontchaillou [Rennes]-Fonction, structure et inactivation d'ARN bactériens, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)-Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes], Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Le Corre, Morgane

Subjects
Male, ARDS, Cytomegalovirus, MESH: Herpes Simplex, law.invention, Cohort Studies, 0302 clinical medicine, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Intensive Care Unit Admission, Simplexvirus, 030212 general & internal medicine, Simplified Acute Physiology Score, Acute Respiratory Distress Syndrome, MESH: Cohort Studies, MESH: Aged, 0303 health sciences, Univariate analysis, MESH: Middle Aged, medicine.diagnostic_test, Coinfection, Pneumonia, Pneumocystis, General Medicine, Middle Aged, Intensive care unit, 3. Good health, Infectious Diseases, Cytomegalovirus Infections, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, Bronchoalveolar Lavage Fluid, Human Immunodeficiency Virus, Microbiology (medical), medicine.medical_specialty, MESH: Cytomegalovirus, Intensive Care Unit, Article, 03 medical and health sciences, Internal medicine, medicine, Humans, MESH: Simplexvirus, Aged, Retrospective Studies, MESH: Humans, 030306 microbiology, business.industry, MESH: Bronchoalveolar Lavage Fluid, Retrospective cohort study, Herpes Simplex, MESH: Retrospective Studies, Odds ratio, MESH: Cytomegalovirus Infections, medicine.disease, MESH: Male, Herpes Simplex Virus, MESH: Coinfection, Pneumonia, Bronchoalveolar lavage, Immunology, business, MESH: Female, MESH: Pneumonia, Pneumocystis
Abstract

International audience; The purpose of this investigation was to characterize the management and prognosis of severe Pneumocystis jirovecii pneumonia (PJP) in human immunodeficiency virus (HIV)-negative patients. An observational cohort study of HIV-negative adults with PJP documented by bronchoalveolar lavage (BAL) through Gomori-Grocott staining or immunofluorescence, admitted to one intensive care unit (ICU) for acute respiratory failure, was undertaken. From 1990 to 2010, 70 patients (24 females, 46 males) were included, with a mean age of 58.6 ± 18.3 years. The mean Simplified Acute Physiology Score (SAPS)-II was 36.9 ± 20.4. Underlying conditions included hematologic malignancies (n = 21), vasculitis (n = 13), and solid tumors (n = 13). Most patients were receiving systemic corticosteroids (n = 63) and cytotoxic drugs (n = 51). Not a single patient received trimethoprim-sulfamethoxazole as PJP prophylaxis. Endotracheal intubation (ETI) was required in 42 patients (60.0 %), including 38 with acute respiratory distress syndrome (ARDS). In-ICU mortality was 52.9 % overall, reaching 80.9 % and 86.8 %, respectively, for patients who required ETI and for patients with ARDS. In the univariate analysis, in-ICU mortality was associated with SAPS-II (p = 0.0131), ARDS (p

Published
2013
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13. Maintenance of cytomegalovirus-specific CD4pos T-cell response in rheumatoid arthritis patients receiving anti-tumor necrosis factor treatments

Author

Jean-Luc Davignon, Delphine Nigon, Arnaud Constantin, Jean-Frédéric Boyer, Alain Cantagrel, B. Jamard, Service de rhumatologie, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), 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), Epidémiologie et Analyses en Santé Publique : risques, maladies chroniques et handicap (LEASP), Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by Société Française de Rhumatologie and University Paul Sabatier Toulouse III., BMC, Ed., Centre de Rhumatologie [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)

Subjects
CD4-Positive T-Lymphocytes, Male, MESH: Antigens, CD28, Arthritis, Arthritis, Rheumatoid, 0302 clinical medicine, MESH: Aged, 80 and over, Interferon, MESH: Immunocompromised Host, Immunology and Allergy, Interferon gamma, Antigens, Viral, Aged, 80 and over, MESH: Aged, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, 0303 health sciences, MESH: Arthritis, Rheumatoid, MESH: Middle Aged, MESH: CD4-Positive T-Lymphocytes, Middle Aged, 3. Good health, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Rheumatoid arthritis, Cytomegalovirus Infections, MESH: Cell Division, Tumor necrosis factor alpha, Female, MESH: Immunosuppressive Agents, MESH: Antigens, Viral, Cell Division, Immunosuppressive Agents, medicine.drug, Research Article, Adult, MESH: Interferon-gamma, Immunology, Congenital cytomegalovirus infection, 03 medical and health sciences, Immunocompromised Host, Interferon-gamma, Antigen, CD28 Antigens, Rheumatology, Immunity, medicine, Humans, 030304 developmental biology, Aged, 030203 arthritis & rheumatology, MESH: Humans, business.industry, Tumor Necrosis Factor-alpha, MESH: Adult, MESH: Cytomegalovirus Infections, medicine.disease, MESH: Male, MESH: Tumor Necrosis Factor-alpha, business, MESH: Female
Abstract

International audience; INTRODUCTION: Anti-tumor necrosis factor (TNF)-α biotherapies have considerably changed the treatment of rheumatoid arthritis (RA). However, serious infections are a major concern in patients with rheumatic diseases treated with anti-TNF-α. Little is known about viral, especially latent, infections in anti-TNF-α treatments. Infections by cytomegalovirus (CMV), a β-herpes virus, are frequent and induce a strong CD4pos T-cell immunity, which participates in the control of infection. We thus have chosen to analyze the CD4pos T-cell response to CMV antigens as a model of antiviral response in RA patients treated with anti-TNF-α. CD28 expression was evaluated. METHODS: We have measured the CD4pos response to CMV antigens in RA patients, before and after initiation of treatment with an anti-TNF-α agent. The intracellular production of interferon (IFN)-γ in total and CD28neg CD4pos T cells in response to CMV antigens (Ags) was evaluated with flow cytometry. The proliferation of total CD4pos T cells in the presence of CMV antigens was measured with 3H-thymidine incorporation. RESULTS: Anti-TNF-α treatments impaired neither the anti-CD4pos anti-CMV IFN-γ response nor the proliferative response in patients. The percentage of CD28neg CD4pos cells remained constant. CONCLUSIONS: Our data suggest that the CD4pos T-cell response against CMV is not altered by anti-TNF-α treatments and that infection remains controlled in treated RA patients latently infected with CMV. Our observation brings new insight into the current knowledge of the risks of infection in patients treated with anti-TNF-α biotherapies.

Published
2010
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14. Evidence of premature immune aging in patients thymectomized during early childhood

Author

Christophe Ferrand, Solène Fastenackels, Anne Duperrier, Martin Larsen, Delphine Sauce, Beatrix Grubeck-Loebenstein, Michael Keller, Patrice Debré, Daniel Sidi, Victor Appay, Immunité et Infection, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institute for Biomedical Aging Research, Austrian Academy of Sciences (OeAW), Service de cardiologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This work was supported by an INSERM AVENIR grant, the French ANRS, Sidaction, and the European program AutoCell (LSHP-CT-2005-018953)., European Project, Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), USDA Forest Service, Leopold Franzens Universität Innsbruck - University of Innsbruck, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), International Research Center of Medical Sciences (IRCMS), Kumamoto University, Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), University of Innsbruck, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Saas, Philippe, European program AutoCell (LSHP-CT-2005-018953) - INCOMING, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR113-Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])

Subjects
Naive T cell, [SDV.IMM] Life Sciences [q-bio]/Immunology, T cell, medicine.medical_treatment, [SDV]Life Sciences [q-bio], MESH: T-Lymphocyte Subsets, Biology, 03 medical and health sciences, 0302 clinical medicine, Immune system, MESH: Aged, 80 and over, medicine, MESH: Thymectomy, MESH: Aging, Early childhood, Young adult, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, MESH: Adolescent, MESH: Aged, 0303 health sciences, MESH: Cytokines, MESH: Humans, MESH: Immune System, MESH: Middle Aged, MESH: Infant, Newborn, MESH: Child, Preschool, MESH: CD4-Positive T-Lymphocytes, MESH: Adult, General Medicine, MESH: Cytomegalovirus Infections, Phenotype, MESH: CD8-Positive T-Lymphocytes, 3. Good health, Thymectomy, medicine.anatomical_structure, MESH: Young Adult, Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, CD8, 030215 immunology
Abstract

International audience; While the thymus is known to be essential for the initial production of T cells during early life, its contribution to immune development remains a matter of debate. In fact, during cardiac surgery in newborns, the thymus is completely resected to enable better access to the heart to correct congenital heart defects, suggesting that it may be dispensable during childhood and adulthood. Here, we show that young adults thymectomized during early childhood exhibit an altered T cell compartment. Specifically, absolute CD4+ and CD8+ T cell counts were decreased, and these T cell populations showed substantial loss of naive cells and accumulation of oligoclonal memory cells. A subgroup of these young patients (22 years old) exhibited a particularly altered T cell profile that is usually seen in elderly individuals (more than 75 years old). This condition was directly related to CMV infection and the induction of strong CMV-specific T cell responses, which may exhaust the naive T cell pool in the absence of adequate T cell renewal from the thymus. Together, these marked immunological alterations are reminiscent of the immune risk phenotype, which is defined by a cluster of immune markers predictive of increased mortality in the elderly. Overall, our data highlight the importance of the thymus in maintaining the integrity of T cell immunity during adult life.

Published
2009
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15. Structural bases for the affinity-driven selection of a public TCR against a dominant human cytomegalovirus epitope

Author

Xavier Saulquin, E. Debeaupuis, François Legoux, Madalen Le Gorrec, Adrien Kissenpfennig, Paul Machillot, B. Neveu, Jean-Baptiste Reiser, Marc Bonneville, Stephanie Gras, Dominique Housset, Nicole M. Thielens, Bernard Malissen, Anne Chouquet, Klara Echasserieau, Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Recherches en cancérologie, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)

Subjects
Human cytomegalovirus, Amino Acid Motifs, Cytomegalovirus, Epitopes, T-Lymphocyte, Crystallography, X-Ray, Lymphocyte Activation, Epitope, MESH: Virus Activation, MESH: Amino Acid Motifs, 0302 clinical medicine, Immunology and Allergy, Cytotoxic T cell, Medicine(all), Genetics, 0303 health sciences, MESH: Peptides, MESH: Receptors, Antigen, T-Cell, medicine.anatomical_structure, Cytomegalovirus Infections, [SDV.IMM]Life Sciences [q-bio]/Immunology, Protein Binding, MESH: Cytomegalovirus, T cell, Immunology, Receptors, Antigen, T-Cell, MESH: Immunodominant Epitopes, chemical and pharmacologic phenomena, Biology, Major histocompatibility complex, MESH: Phosphoproteins, Viral Matrix Proteins, MESH: Epitopes, T-Lymphocyte, 03 medical and health sciences, Antigen, HLA-A2 Antigen, medicine, Humans, MESH: Protein Binding, MESH: Lymphocyte Activation, MESH: HLA-A Antigens, 030304 developmental biology, MESH: Viral Matrix Proteins, MESH: Humans, HLA-A Antigens, Immunodominant Epitopes, T-cell receptor, MESH: Clone Cells, MESH: Cytomegalovirus Infections, Phosphoproteins, medicine.disease, MESH: Crystallography, X-Ray, Clone Cells, Transplantation, biology.protein, Virus Activation, Peptides, 030215 immunology
Abstract

Protective T cell responses elicited along chronic human CMV (HCMV) infections are sometimes dominated by CD8 T cell clones bearing highly related or identical public TCR in unrelated individuals. To understand the principles that guide emergence of these public T cell responses, we have performed structural, biophysical, and functional analyses of an immunodominant public TCR (RA14) directed against a major HLA-A*0201-restricted HCMV Ag (pp65495–503) and selected in vivo from a diverse repertoire after chronic stimulations. Unlike the two immunodominant public TCRs crystallized so far, which focused on one peptide hotspot, the HCMV-specific RA14 TCR interacts with the full array of available peptide residues. The conservation of some peptide-MHC complex-contacting amino acids by lower-affinity TCRs suggests a shared TCR-peptide-MHC complex docking mode and supports an Ag-driven selection of optimal TCRs. Therefore, the emergence of a public TCR of an oligoclonal Ag-specific response after repeated viral stimulations is based on a receptor displaying a high structural complementarity with the entire peptide and focusing on three peptide hotspots. This highlights key parameters underlying the selection of a protective T cell response against HCMV infection, which remains a major health issue in patients undergoing bone marrow transplantation.

Published
2009
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16. Cytomegalovirus microRNAs

Author

Lars Dölken, Sébastien Pfeffer, Ulrich H. Koszinowski, Max Von Pettenkofer Institute (MVP), Ludwig-Maximilians-Universität München (LMU), Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Gene Expression Regulation, Viral, MESH: Cytomegalovirus, Pan troglodytes, viruses, Cytomegalovirus, MESH: Pan troglodytes, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Mice, 03 medical and health sciences, MESH: Gene Expression Regulation, Viral, 0302 clinical medicine, Virology, Genetics, Animals, Humans, MESH: Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, MESH: Mice, HCMV, 030304 developmental biology, miRNA, 0303 health sciences, MESH: Humans, CCMV, virus diseases, Herpesvirus, General Medicine, MESH: Cytomegalovirus Infections, 3. Good health, MicroRNAs, 030220 oncology & carcinogenesis, Cytomegalovirus Infections, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: MicroRNAs, MCMV
Abstract

International audience; MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression at a post-transcriptional level in virtually all eukaryotic organisms and some viruses, particularly herpesviruses. miRNAs are non-immunogenic, stealthy tools for viruses to regulate their as well as host gene expression. The human cytomegalovirus (HCMV) is the major cause of morbidity in immunocompromised patients and allogenic bone-marrow or organ-transplant recipients and the leading cause of congenital birth defects. HCMV miRNAs may provide valuable targets for new urgently needed antiviral drugs. This review focuses on recent findings for viral miRNAs expressed by cytomegaloviruses (CMV) including data from human, chimpanzee, and murine CMV. These are discussed in the context of findings for other viruses to highlight potentially conserved roles exerted by viral miRNAs.

Published
2009
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17. Direct genotyping of cytomegalovirus envelope glycoproteins from toddler's saliva samples

Author

Jérôme Grosjean, P. Brosset, François Denis, Sébastien Hantz, Sophie Alain, F. Undreiner, C. Pasquier, L. Trapes, B. Virey, Marie-Claire Baclet, Catherine Mengelle, Sébastien Cotin, Biologie moléculaire et cellulaire des microorganismes (EA3175), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Bactériologie, Virologie, Hygiène [CHU Limoges], CHU Limoges, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), 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), Service de Pédiatrie médicale [CHU Limoges], Association Française de Pédiatrie Ambulatoire (AFPA), and Raherison, Sophie

Subjects
Human cytomegalovirus, Saliva, MESH: Child Day Care Centers, Cytomegalovirus, Polymerase Chain Reaction, law.invention, MESH: Genotype, 0302 clinical medicine, Viral Envelope Proteins, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, law, Genotype, 030212 general & internal medicine, Polymerase chain reaction, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Infectivity, Genetics, 0303 health sciences, MESH: Polymorphism, Single Nucleotide, MESH: Infant, 3. Good health, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Cytomegalovirus Infections, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Restriction fragment length polymorphism, Polymorphism, Restriction Fragment Length, MESH: Cytomegalovirus, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, Viral Proteins, Virology, medicine, Humans, MESH: Saliva, Typing, Genotyping, 030304 developmental biology, MESH: Humans, MESH: Polymorphism, Restriction Fragment Length, Infant, MESH: Polymerase Chain Reaction, MESH: Cytomegalovirus Infections, Child Day Care Centers, medicine.disease, MESH: Viral Proteins, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Viral Envelope Proteins, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract

Centre Hospitalier Universitaire (CHU) Limoges, Centre National de Reference du CMV, Laboratoire de Bactériologie-Virologie-Hygiène, Limoges, France; International audience; BACKGROUND: The polymorphism of genes encoding CMV envelope protein is used for strain classification and may influence pathogenesis and/or infectivity. CMV genotyping is usually based on sequencing or acrylamide gel-RFLP, but these methods are not suited to rapid screening of large populations. OBJECTIVES: We developed a high-throughput method to analyze CMV strains diversity and to detect multiple-strain infection in a large population of toddlers (six daycare centers (DCC) and an emergency unit (EU)). METHODS: We developed a new PCR-RFLP method coupled with capillary electrophoresis fragment detection for UL55-gB, UL75-gH and UL73-gN genotyping. To detect gB recombinants, gpUL55 typing was applied to two variable zones (NTerminal and central). We applied this method to 212 CMV-positive saliva samples and controlled the results by direct sequencing of PCR products. RESULTS: We identified 112 strains, that fell into eight groups in UL55-gB, two groups in UL75-gH, and seven groups in UL73-gN. The 79 samples from the emergency unit contained 30 strains, 28 children harboring 2 strains. The samples (n=133) from the six daycare centers contained respectively 4, 1, 6, 1 and 11 strains. Fifteen percent of strains were UL55-gB recombinants. CONCLUSION: Our new method can simultaneously determine gB, gH and gN genotypes and offers more precise classification of CMV strains than previous RFLP-based methods. This could constitute the basis for a new classification, particularly in UL55-gB. Easy direct identification of multiple strains and recombinants in pathological samples could facilitate large epidemiologic studies.

Published
2009
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18. Rapid determination of antiviral drug susceptibility of human cytomegalovirus by real-time PCR

Author

Marie-Christine Mazeron, Marie-José Sanson-Le Pors, Françoise Petit, Sophie Alain, Nicolas Boiteau, Nathalie Schnepf, Biologie moléculaire et cellulaire des microorganismes (EA3175), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Limoges (UNILIM), Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)

Subjects
Foscarnet, Human cytomegalovirus, viruses, Cytomegalovirus, MESH: DNA Replication, Viral Plaque Assay, Polymerase Chain Reaction, chemistry.chemical_compound, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Cells, Cultured, 0303 health sciences, virus diseases, 3. Good health, MESH: Reproducibility of Results, Real-time polymerase chain reaction, Cytomegalovirus Infections, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, medicine.drug, Cidofovir, MESH: Cells, Cultured, DNA Replication, Ganciclovir, MESH: Antiviral Agents, MESH: Plaque Assay, MESH: Cytomegalovirus, medicine.drug_class, Congenital cytomegalovirus infection, Biology, Antiviral Agents, 03 medical and health sciences, Virology, medicine, Humans, 030304 developmental biology, Pharmacology, MESH: Humans, 030306 microbiology, Reproducibility of Results, MESH: Polymerase Chain Reaction, MESH: Cytomegalovirus Infections, biochemical phenomena, metabolism, and nutrition, medicine.disease, Molecular biology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: DNA, Viral, chemistry, DNA, Viral, Antiviral drug
Abstract

International audience; A quantitative real-time PCR-based assay was developed for determination of cytomegalovirus (HCMV) susceptibility to antiviral drugs. After HCMV isolate-growth for 4 days, antiviral drug susceptibility was determined by measuring the reduction of intracellular HCMV DNA in the presence of increasing concentrations of either ganciclovir, or foscarnet or cidofovir. The 50% inhibitory concentration (IC(50)) was the drug concentration that reduced the number of HCMV genome copies by 50%. The IC(50) values were measured for seven HCMV reference strains sensitive or resistant to one or more antiviral drugs. The antiviral susceptibility of 21 HCMV isolates was then tested and the results were consistent with prior determination of their phenotype and/or genotype by plaque reduction assay and sequencing. The real-time PCR susceptibility assay reported here was found to be highly reproducible, simpler to perform than the plaque reduction assay, and amenable to use in the routine diagnostic virology laboratory.

Published
2009
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19. [Cytomegalovirus and cryptogenic inflammatory bowel disease]

Author

Pofelski, Joanna, Heluwaert, Frédéric, Roblin, Xavier, Morand, Patrice, Gratacap, Bénédicte, Germain, Emmanuel, Brion, Jean-Paul, Salon, Caroline, Bonaz, Bruno, Sinniger, Valérie, Service d'hépato-gastroentérologie, CHU Grenoble, Laboratoire de virologie moléculaire et structurale, Département de médecine aiguë spécialisée, CHU Grenoble-Hôpital Michallon, and Département d'anatomo-pathologie

Subjects
MESH: Antiviral Agents, MESH: Cytomegalovirus, MESH: Humans, MESH: Immunologic Factors, MESH: Virus Replication, Cytomegalovirus, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH: Cytomegalovirus Infections, MESH: Inflammatory Bowel Diseases, Inflammatory Bowel Diseases, Virus Replication, digestive system, Antiviral Agents, digestive system diseases, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Cytomegalovirus Infections, Humans, Immunologic Factors
Abstract

International audience; CMV infection has been reported in association with some flares of IBD. Its prevalence varies with the method of diagnosis and the severity of IBD. Although the link between CMV and IBD is not clear, the immunomodulator properties of the virus may play a role in the evolution of IBD. Besides the necessity of immunosuppression to treat IBD, inflammation per se can maintain in situ viral replication. Antiviral treatment can be useful in some situations. New molecular methods will permit earlier and more sensitive diagnosis of CMV infection and a better evaluation of treatment efficacy.

Published
2007

20. [Management of severe or corticosteroid resistant ulcerative colitis]

Author

Carbonnel, Franck, Humbert, Murielle, Agents pathogènes et inflammation - UFC (EA 4266) (API), Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)

Subjects
MESH: Antiviral Agents, Time Factors, Anti-Inflammatory Agents, Drug Resistance, MESH: Colitis, Ulcerative, Antiviral Agents, MESH: Cyclosporine, MESH: Antibodies, Monoclonal, Gastrointestinal Agents, Humans, Multicenter Studies as Topic, Prospective Studies, Radionuclide Imaging, Ganciclovir, Colectomy, ComputingMilieux_MISCELLANEOUS, Randomized Controlled Trials as Topic, MESH: Colectomy, MESH: Humans, MESH: Time Factors, Antibodies, Monoclonal, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH: Cytomegalovirus Infections, MESH: Gastrointestinal Agents, Infliximab, MESH: Prospective Studies, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH: Randomized Controlled Trials as Topic, MESH: Anti-Inflammatory Agents, Cytomegalovirus Infections, MESH: Ganciclovir, Cyclosporine, MESH: Multicenter Studies as Topic, MESH: Drug Resistance, Colitis, Ulcerative, MESH: Immunosuppressive Agents, Immunosuppressive Agents, Foscarnet, MESH: Foscarnet
Abstract

National audience

Published
2007

21. Monitoring human cytomegalovirus (HCMV) in HCMV-seropositive orthotopic liver-transplant recipients by means of quantitative real-time polymerase chain reaction

Author

Mengelle, Catherine, Legrand-Abravanel, Florence, Kamar, Nassim, Alain, Sophie, Basse, Grégoire, Pillet, Adèle, Lavayssière, Laurence, Suc, Bertrand, Izopet, Jacques, Rostaing, Lionel, Université de Limoges (UNILIM), Biologie moléculaire et cellulaire des microorganismes (EA3175), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Bucek, Ingrid

Subjects
Graft Rejection, MESH: Cytomegalovirus, MESH: Liver Transplantation, Time Factors, Cytomegalovirus, MESH: Graft Rejection, MESH: Creatinine, Polymerase Chain Reaction, Postoperative Complications, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Postoperative Complications, Humans, Retrospective Studies, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Humans, MESH: Time Factors, virus diseases, MESH: Polymerase Chain Reaction, MESH: Retrospective Studies, MESH: Cytomegalovirus Infections, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Liver Transplantation, Creatinine, Cytomegalovirus Infections, Epidemiological Monitoring, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Environmental Monitoring, Environmental Monitoring
Abstract

International audience; OBJECTIVE: Human cytomegalovirus can be reactivated after orthotopic liver transplantation in patients who are seropositive for cytomegalovirus. Whether those cytomegalovirus-seropositive patients require immediate posttransplant (anti)- cytomegalovirus prophylactic therapy or preemptive treatment as opposed to deferred treatment remains controversial. The aims of our study were to evaluate the relevance of cytomegalovirus monitoring with quantitative real-time polymerase chain reaction in whole blood and to analyze the factors that determine the treatment of the first episode of cytomegalovirus infection with intravenous ganciclovir in seropositive liver-transplant patients. PATIENTS AND METHODS: Forty-two cytomegalovirus-seropositive liver-transplant patients were assessed for cytomegalovirus DNAemia every 2 weeks until posttransplant day 90 and every 3 to 4 weeks until day 180. Biochemical and hematologic parameters were also prospectively monitored. RESULTS: Cytomegalovirus DNAemia was detected at least once in 27 patients (64%). Treatment was initiated in 12 patients (group 1) but not in 15 others (group 2). Median HCMV viral loads of the first positive and the highest DNAemia were statistically higher in group 1 than in group 2 (P = 0.01). Univariate analysis of DNAemia showed that alkaline phosphatase levels were significantly higher in group 1 than in group 2 (P = .0011) and that hemoglobin levels were significantly lower in group 1 than in group 2 (P = .0443). The results of multivariate analysis showed that the only factor that predicted the treatment of the first episode of HCMV DNAemia was a level of alkaline phosphatase greater than 150 IU/L [odds ratio, 20; range, 1.97-203.32; P = .01]. CONCLUSIONS: A combination of criteria, including viral-load kinetics, clinical factors, alkaline phosphatase levels (in particular), and the patient's immune condition, is required to efficiently monitor patients who are seropositive for cytomegalovirus after orthotopic liver transplantation.

Published
2006

22. Cytomegalovirus prophylaxis with intravenous polyvalent immunoglobulin in high-risk renal transplant recipients

Author

Estelle Desport, Franck Bridoux, R. Abou Ayache, Guy Touchard, Fannie Leroy, Anne Sechet, Antoine Thierry, Simohamed Belmouaz, Marc Bauwens, Centre Interdisciplinaire de Nanoscience de Marseille (CINaM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Etudes Aérodynamiques (LEA), Centre National de la Recherche Scientifique (CNRS)-ENSMA-Université de Poitiers, Science et Technologie du Lait et de l'Oeuf (STLO), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, and Université de Poitiers-ENSMA-Centre National de la Recherche Scientifique (CNRS)

Subjects
Human cytomegalovirus, medicine.medical_specialty, Opportunistic infection, Urinary system, Congenital cytomegalovirus infection, 030204 cardiovascular system & hematology, Asymptomatic, Gastroenterology, MESH: Kidney Transplantation, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Recurrence, Risk Factors, Betaherpesvirinae, MESH: Risk Factors, Internal medicine, MESH: Postoperative Complications, medicine, Humans, 030212 general & internal medicine, MESH: Immunoglobulins, Intravenous, Infusions, Intravenous, MESH: Infusions, Intravenous, Retrospective Studies, Transplantation, Kidney, MESH: Humans, biology, business.industry, Immunoglobulins, Intravenous, virus diseases, MESH: Retrospective Studies, MESH: Cytomegalovirus Infections, medicine.disease, biology.organism_classification, Kidney Transplantation, 3. Good health, Surgery, MESH: Recurrence, medicine.anatomical_structure, Cytomegalovirus Infections, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.symptom, business
Abstract

International audience; Cytomegalovirus (CMV) seronegative renal allograft recipients (R-), particularly those with a graft from a CMV-seropositive donor (D+), are at high risk for primary CMV infection. CMV resistance to antiviral oral therapy is an emerging problem in renal transplantation, prompting development of new prophylactic strategies. We retrospectively studied the 1-year posttransplantation incidence of CMV infection in high-risk renal transplant recipients, in whom polyvalent intravenous immunoglobulins (IVIg) were used as prophylaxis. Forty R- patients received immunoprophylaxis by polyvalent IVIg (0.25 g/kg weekly for 8 weeks, starting on the operative day). CMV serological tests remained negative in eight patients (20%). Eight patients (20%) had asymptomatic CMV infection while 24 (60%) developed CMV syndrome and were treated with gancyclovir (10 mg/kg/day intravenously for 3 weeks). None had CMV disease or opportunistic infection. Six patients (15%) had biopsy-proven acute rejection, which followed CMV syndrome in three cases. One-year renal allograft and patient survivals were 95% and 97.5%, respectively. Mean serum creatinine level was 124 +/- 33 micromol/L at 1 year. Clinical tolerance of IVIg was excellent, without any episode of acute renal failure. Polyvalent IVIg provides effective prophylaxis in renal transplant recipients at high risk for CMV infection and is associated with excellent 1-year allograft survival. Because of their immunomodulatory functions, IVIg may have a beneficial effect on the incidence of acute and chronic rejection and allograft survival. A randomized prospective study is required to evaluate long-term effects of CMV prophylaxis with polyvalent IVIg compared to antiviral agents in renal transplant recipients.

Published
2006
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23. Reprogramming of CTLs into natural killer-like cells in celiac disease

Author

Veronique M. Braud, Gerasim A. Orbelyan, Cezary Ciszewski, Bana Jabri, Daniel E. Geraghty, Peter H.R. Green, Govind Bhagat, Carol E. Semrad, Emily O. Kistner, Robert Winchester, Stefano Guandalini, Maria Tretiakova, Bertrand Meresse, Mala Setty, Leanne Lee, Lewis L. Lanier, Shane A. Curran, University of Chicago, Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Columbia University [New York], COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), University of California SF (UNIVERSITY OF CALIFORNIA), University of California, and Fred Hutchinson Cancer Research Center [Seattle] (FHCRC)

Subjects
MESH: Signal Transduction, MESH: Intestine, Small, Lymphoma, MESH: Base Sequence, 0302 clinical medicine, Intestinal mucosa, Interferon, Intestine, Small, Immunology and Allergy, Cytotoxic T cell, Interferon gamma, Intestinal Mucosa, Phosphorylation, Receptors, Immunologic, Receptor, 0303 health sciences, ZAP-70 Protein-Tyrosine Kinase, Cell Differentiation, hemic and immune systems, Articles, MESH: Gene Expression Regulation, 3. Good health, Killer Cells, Natural, Cytomegalovirus Infections, MESH: Intestinal Mucosa, Signal transduction, medicine.drug, Signal Transduction, MESH: Killer Cells, Natural, MESH: Cell Differentiation, MESH: Interferon Type II, Immunology, Molecular Sequence Data, chemical and pharmacologic phenomena, Biology, Article, 03 medical and health sciences, Interferon-gamma, MESH: Gene Expression Profiling, MESH: Cell Proliferation, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Receptors, Immunologic, 030304 developmental biology, Cell Proliferation, MESH: Molecular Sequence Data, MESH: Humans, Base Sequence, MESH: Phosphorylation, Gene Expression Profiling, MESH: Chronic Disease, MESH: ZAP-70 Protein-Tyrosine Kinase, MESH: Cytomegalovirus Infections, CTL, Celiac Disease, Gene Expression Regulation, MESH: Protein Processing, Post-Translational, Chronic Disease, Cytokine secretion, MESH: Lymphoma, Protein Processing, Post-Translational, MESH: T-Lymphocytes, Cytotoxic, MESH: Celiac Disease, 030215 immunology, T-Lymphocytes, Cytotoxic
Abstract

Celiac disease is an intestinal inflammatory disorder induced by dietary gluten in genetically susceptible individuals. The mechanisms underlying the massive expansion of interferon γ–producing intraepithelial cytotoxic T lymphocytes (CTLs) and the destruction of the epithelial cells lining the small intestine of celiac patients have remained elusive. We report massive oligoclonal expansions of intraepithelial CTLs that exhibit a profound genetic reprogramming of natural killer (NK) functions. These CTLs aberrantly expressed cytolytic NK lineage receptors, such as NKG2C, NKp44, and NKp46, which associate with adaptor molecules bearing immunoreceptor tyrosine-based activation motifs and induce ZAP-70 phosphorylation, cytokine secretion, and proliferation independently of T cell receptor signaling. This NK transformation of CTLs may underlie both the self-perpetuating, gluten-independent tissue damage and the uncontrolled CTL expansion leading to malignant lymphomas in severe forms of celiac disease. Because similar changes were detected in a subset of CTLs from cytomegalovirus-seropositive patients, we suggest that a stepwise transformation of CTLs into NK-like cells may underlie immunopathology in various chronic infectious and inflammatory diseases.

Published
2006
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24. Hypomorphic RAG1 mutations and CMV infection: a new phenotype of severe combined immunodeficiency

Author

Le Deist, Françoise, De Villartay, Jean-Pierre, Lim, Annick, Déchanet-Merville, Julie, Fischer, Alain, Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunité Antivirale, Biothérapie et Vaccins, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Référence Déficits Immunitaires Héréditaires ( CEREDIH ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Composantes innées de la réponse immunitaire et différenciation ( CIRID ), and Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique ( CNRS )

Subjects
MESH: Humans, MESH: Mutation, MESH : Humans, MESH : Severe Combined Immunodeficiency, MESH : Nuclear Proteins, MESH: Severe Combined Immunodeficiency, MESH: Cytomegalovirus Infections, MESH: Phenotype, MESH : Cytomegalovirus Infections, MESH : Phenotype, MESH: Homeodomain Proteins, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : DNA-Binding Proteins, MESH : Homeodomain Proteins, MESH : Mutation, MESH: Nuclear Proteins, MESH: DNA-Binding Proteins
Published
2006
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25. MyD88-dependent and -independent murine cytomegalovirus sensing for IFN-alpha release and initiation of immune responses in vivo

Author

André Paquin, Philippe Kastner, Shizuo Akira, Thomas Delale, Alain Vicari, Giorgio Trinchieri, Géraldine Brizard, Susan Chan, Elizabeth E. M. Bates, Francine Brière, Christine A. Biron, Marc Dalod, Carine Asselin-Paturel, Schering-Plough Laboratories for Immunological Research, Schering Plough Laboratories, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Toussaint, Jean-Luc, and Guglietta, Noëlle

Subjects
Cytotoxicity, Immunologic, MESH: Interleukin-12, Muromegalovirus, medicine.medical_treatment, Plasmacytoid dendritic cell, MESH: Base Sequence, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Antibodies, Viral, MESH: Mice, Knockout, Mice, Immunology and Allergy, Cytotoxic T cell, MESH: Animals, Receptors, Immunologic, Mice, Knockout, MESH: Toll-Like Receptor 9, MESH: Dendritic Cells, MESH: Toll-Like Receptor 2, Cell Differentiation, hemic and immune systems, MESH: Toll-Like Receptor 4, MESH: Toll-Like Receptor 3, Acquired immune system, Interleukin-12, Killer Cells, Natural, Cytokine, Liver, MESH: Antigens, Differentiation, Cytomegalovirus Infections, MESH: Immunoglobulin Class Switching, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH: Interferon-alpha, MESH: Myeloid Differentiation Factor 88, MESH: Killer Cells, Natural, MESH: Cell Differentiation, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Interferon Type II, Immunology, MESH: Muromegalovirus, Biology, Interferon-gamma, Immune system, MESH: Mice, Inbred C57BL, medicine, Animals, MESH: Cytotoxicity, Immunologic, MESH: Mice, MESH: Receptors, Immunologic, Adaptor Proteins, Signal Transducing, MESH: Adaptor Proteins, Signal Transducing, Base Sequence, TLR9, Interferon-alpha, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Dendritic cell, Dendritic Cells, MESH: Cytomegalovirus Infections, Antigens, Differentiation, Immunoglobulin Class Switching, Toll-Like Receptor 2, Toll-Like Receptor 3, MESH: DNA, Viral, Mice, Inbred C57BL, Toll-Like Receptor 4, Immunoglobulin class switching, Toll-Like Receptor 9, DNA, Viral, Myeloid Differentiation Factor 88, MESH: Female, MESH: Antibodies, Viral, MESH: Liver
Abstract

Antiviral immunity requires early and late mechanisms in which IFN-α and IL-12 play major roles. However, the initial events leading to their production remain largely unclear. Given the crucial role of TLR in innate recognition, we investigated their role in antiviral immunity in vivo. Upon murine CMV (MCMV) infection, both MyD88−/− and TLR9−/− mice were more susceptible and presented increased viral loads compared with C57BL/6, TLR2−/−, TLR3−/−, or TLR4−/− mice. However, in terms of resistance to infection, IFN-α production and in many other parameters of early inflammatory responses, the MyD88−/− mice showed a more defective response than TLR9−/− mice. In the absence of the TLR9/MyD88 signaling pathway, cytokine production was dramatically impaired with a complete abolition of bioactive IL-12p70 serum release contrasting with a high flexibility for IFN-α release, which is initially (36 h) plasmacytoid dendritic cell- and MyD88-dependent, and subsequently (44 h) PDC-, MyD88-independent and, most likely, TLR-independent. NK cells from MCMV-infected MyD88−/− and TLR9−/− mice displayed a severely impaired IFN-γ production, yet retained enhanced cytotoxic activity. In addition, dendritic cell activation and critical inflammatory cell trafficking toward the liver were still effective. In the long term, except for isotype switching to MCMV-specific IgG1, the establishment of Ab responses was not significantly altered. Thus, our results demonstrate a critical requirement of TLR9 in the process of MCMV sensing to assure rapid antiviral responses, coordinated with other TLR-dependent and -independent events that are sufficient to establish adaptive immunity.

Published
2005

26. Phenotypic characterisation of cytomegalovirus DNA polymerase: a method to study cytomegalovirus isolates resistant to foscarnet

Author

Marie-José Sanson-Le Pors, Jérôme Gravisse, Marie-Christine Mazeron, Anne-Marie Fillet, Françoise Petit, Sophie Alain, Alexandra Ducancelle, Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Biologie moléculaire et cellulaire des microorganismes (EA3175), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Limoges (UNILIM), Service de virologie [CHU Pitié-Salpêtrière], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP]

Subjects
Human cytomegalovirus, Foscarnet, MESH: Cytomegalovirus, DNA polymerase, Cytomegalovirus, DNA-Directed DNA Polymerase, 03 medical and health sciences, chemistry.chemical_compound, Transcription (biology), [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, Drug Resistance, Viral, MESH: DNA-Directed DNA Polymerase, medicine, MESH: Genetic Variation, Gene, Polymerase, 030304 developmental biology, 0303 health sciences, Expression vector, MESH: Drug Resistance, Viral, biology, 030306 microbiology, Genetic Variation, virus diseases, MESH: Cytomegalovirus Infections, biochemical phenomena, metabolism, and nutrition, medicine.disease, Molecular biology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, chemistry, Cytomegalovirus Infections, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology.protein, DNA, medicine.drug, MESH: Foscarnet
Abstract

International audience; A phenotypic method was developed to test mutations in the human cytomegalovirus (HCMV) DNA polymerase gene (UL54) suspected to confer resistance to foscarnet. This method was used to determine the biochemical phenotype of wild-type and mutated HCMV DNA polymerases that had been synthesised in vitro as follows. The UL54 genes were amplified from foscarnet-resistant and -sensitive isolates by PCR and the products were cloned into an expression vector under the control of a T7 promoter. Mutations were introduced by site-directed mutagenesis into wild-type gene UL54 and then polymerases were synthesised by using a commercially available coupled transcription/translation system. Polymerase activity was measured with and without foscarnet by detecting the incorporation of digoxigenin-labelled nucleotides into the growing DNA chain. The results of this non-radioactive assay were consistent with those obtained with the conventional radioactive assay. It was found that the activity of polymerases containing the V715M or E756K mutations was inhibited by foscarnet at concentrations 70- and 30-fold higher than that of wild-type polymerase, respectively. Change N495K and a combination of changes K415R and S291P, both observed in foscarnet-resistant isolates, induced a 5- and 10-fold decrease in susceptibility to foscarnet, respectively. This non-radioactive phenotypic assay could be useful for the characterisation of mutations that confer HCMV resistance to foscarnet.

Published
2005
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27. Cytomegalovirus infection in patients with active inflammatory bowel disease

Author

Marie-José Sanson-Le Pors, Philippe de Saussure, Yoram Bouhnik, Marie-Christine Mazeron, Sophie Alain, Anne Lavergne, Alexandra Ducancelle, Université de Limoges (UNILIM), Biologie moléculaire et cellulaire des microorganismes (EA3175), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7)

Subjects
Messenger ribonucleic acid, Adult, Male, Nucleic acid sequence based amplification, Congenital cytomegalovirus infection, MESH: Colitis, Ulcerative, Inflammatory bowel disease, Immunoglobulin G, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, medicine, Humans, In patient, ComputingMilieux_MISCELLANEOUS, Aged, MESH: Aged, MESH: Humans, MESH: Middle Aged, biology, MESH: Adult, MESH: Cytomegalovirus Infections, Middle Aged, medicine.disease, MESH: Inflammatory Bowel Diseases, Inflammatory Bowel Diseases, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Male, Cytomegalovirus infection, Infectious Diseases, Immunoglobulin M, 030220 oncology & carcinogenesis, Immunology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Cytomegalovirus Infections, biology.protein, 030211 gastroenterology & hepatology, Colitis, Ulcerative, Female, MESH: Female
Abstract

International audience

Published
2005
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28. Inferring behavior from functional brain images

Author

Denis Le Bihan, Stanislas Dehaene, Pierre-Francois Van de Moortele, Jean-Baptiste Poline, Gurvan Le Clec'H, Laurent D. Cohen, Service NEUROSPIN (NEUROSPIN), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), IFR de Neuroimagerie Fonctionnelle (IFR 49), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
[SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, media_common.quotation_subject, MESH: Motor Cortex, Functional Laterality, Task (project management), MESH: Magnetic Resonance Imaging, 03 medical and health sciences, Functional brain, 0302 clinical medicine, Neuroimaging, medicine, Humans, MESH: Functional Laterality, Function (engineering), ComputingMilieux_MISCELLANEOUS, MESH: Brain Mapping, 030304 developmental biology, media_common, Brain Mapping, 0303 health sciences, MESH: Humans, Basis (linear algebra), Resting state fMRI, MESH: Bronchopneumonia, General Neuroscience, Brain morphometry, MESH: Infant, Newborn, Motor Cortex, MESH: Cytomegalovirus Infections, Magnetic Resonance Imaging, MESH: Infant, MESH: Malabsorption Syndromes, medicine.anatomical_structure, MESH: Nerve Net, Nerve Net, MESH: Anemia, Hemolytic, Autoimmune, Psychology, Neuroscience, MESH: Female, 030217 neurology & neurosurgery, Motor cortex
Abstract

Most neuroimaging experiments aim to identify brain areas whose activation correlates tightly with an aspect of the subjects' behavioral task. If the logic of neuroimaging is correct, however, it should also be possible to reverse this sequence of operations. Once we understand the function of a given brain area or network of areas, it should be possible to use on-line activation measurements to infer what kind of task the subject was performing. As a first step in this direction, we report here that functional magnetic resonance images (fMRI) of motor cortex have sufficient signal-to-noise ratio to accurately predict the subject's manual behavior on a single-trial basis with close to 100% accuracy.

Published
1998
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29. Human cytomegalovirus (HCMV) late-mRNA detection in peripheral blood of AIDS patients: diagnostic value for HCMV disease compared with those of viral culture and HCMV DNA detection

Author

J M Salord, Christos Chouaid, Marie-Caroline Meyohas, C Duvivier, Jean-Claude Petit, O Picard, Joël Gozlan, Epidémiologie des maladies infectieuses et modélisation (ESIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Gozlan J, JM Salord, C Chouaïd, Duvivier C, O Picard, Meyohas MC, JC Petit ., and Annesi-Maesano, Isabella

Subjects
Male, Human cytomegalovirus, viruses, Cytomegalovirus, MESH: Base Sequence, medicine.disease_cause, Polymerase Chain Reaction, law.invention, law, Polymerase chain reaction, Viral culture, MESH: AIDS-Related Opportunistic Infections, Evaluation Studies as Topic, MESH: RNA, Viral, Cytomegalovirus Infections, MESH: Evaluation Studies as Topic, RNA, Viral, Female, Viral disease, Research Article, Adult, Microbiology (medical), MESH: Cytomegalovirus, Virus Cultivation, Molecular Sequence Data, Biology, Sensitivity and Specificity, Virus, Herpesviridae, MESH: Virus Cultivation, medicine, Humans, RNA, Messenger, Viremia, MESH: Viremia, MESH: RNA, Messenger, MESH: Molecular Sequence Data, MESH: Humans, AIDS-Related Opportunistic Infections, Base Sequence, MESH: Adult, MESH: Polymerase Chain Reaction, MESH: Cytomegalovirus Infections, medicine.disease, Virology, Reverse transcriptase, MESH: Sensitivity and Specificity, MESH: Male, MESH: DNA, Viral, Viral replication, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, DNA, Viral, Immunology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Female
Abstract

International audience; A reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect a human cytomegalovirus (HCMV) late mRNA in peripheral blood leukocytes (PBL) of 102 human immunodeficiency virus-infected individuals. The clinical value of this new technique for the diagnosis of acute HCMV disease was evaluated in comparison with viral culture and direct amplification of viral DNA (PCR). The sensitivity of the RT-PCR was slightly lower than that of the two other methods, but its specificity was 94%, compared to 55 and 32% for culture and PCR, respectively. Transcription of this late mRNA is linked to viral replication, and its detection in PBL confirms that these cells can support a complete viral cycle. The relationship between complete replicative cycles and HCMV disease makes RT-PCR a useful clinical tool.

Published
1993

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