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15 results on '"Chantal Fournier-Wirth"'

1. Near-point-of-care assay with a visual readout for detection of HIV-1 drug resistance mutations: A proof-of-concept study

Author

Brigitte Montes, Didier Laureillard, Jean-Charles Brès, Chantal Fournier-Wirth, Nicolas Nagot, Vincent Foulongne, Jean-Pierre Molès, Philippe Van de Perre, Julien Gomez-Martinez, Jean-François Cantaloube, Pathogenesis and Control of Chronic and Emerging Infections (PCCEI), Université des Antilles (UA)-Etablissement français du don du sang [Montpellier]-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Laboratoire de Virologie, Centre Hospitalier Universitaire de Montpellier, Montpellier, France.

Subjects
Genotype, Anti-HIV Agents, [SDV]Life Sciences [q-bio], Point-of-Care Systems, HIV Infections, 02 engineering and technology, Drug resistance, 01 natural sciences, Analytical Chemistry, Lateral flow test, symbols.namesake, Drug Resistance, Viral, medicine, Humans, Multiplex, ComputingMilieux_MISCELLANEOUS, Sanger sequencing, Reverse-transcriptase inhibitor, Chemistry, Transmission (medicine), 010401 analytical chemistry, 021001 nanoscience & nanotechnology, Virology, 0104 chemical sciences, 3. Good health, Mutation, symbols, HIV-1, DNA microarray, 0210 nano-technology, HIV drug resistance, medicine.drug
Abstract

Human immunodeficiency virus (HIV) infection is a chronic disease that can be treated with antiretroviral (ARV) therapy. However, the success of this treatment has been jeopardized by the emergence of HIV infections resistant to ARV drugs. In low-to middle-income countries (LMICs), where transmission of resistant viruses has increased over the past decade, there is an urgent need to improve access to HIV drug resistance testing. Here, we present a proof-of-concept study of a rapid and simple molecular method to detect two major mutations (K103 N, Y181C) conferring resistance to first-line nonnucleoside reverse transcriptase inhibitor regimens. Our near-point-of-care (near-POC) diagnostic test, combining a sequence-specific primer extension and a lateral flow DNA microarray strip, allows visual detection of HIV drug resistance mutations (DRM) in a short turnaround time (4 h 30). The assay has a limit of detection of 100 copies of plasmid DNA and has a higher sensitivity than standard Sanger sequencing. The analytical performance was assessed by use of 16 plasma samples from individuals living with HIV-1 and results demonstrated the specificity and the sensitivity of this approach for multiplex detection of the two DRMs in a single test. Furthermore, this near-POC assay could be easily taylored to detect either new DRMs or DRM of from various HIV clades and might be useful for pre-therapy screening in LMICs with high levels of transmitted drug resistance.

Published
2021
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2. Diagnostic Performance of a Magnetic Field-Enhanced Agglutination Readout in Detecting Either Viral Genomes or Host Antibodies in Arbovirus Infection

Author

Jean-Jacques Vasseur, Elena Pinchon, Nevzat Temurok, Fanny Leon, Chantal Fournier-Wirth, Aurélien Daynes, Martine Clot, Vincent Foulongne, Philippe Van de Perre, François Morvan, Jean-François Cantaloube, Jean-Pierre Molès, Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), HORIBA Medical (HORIBA ABX SAS), HORIBA Scientific [France], Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), 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), Pathogenesis and Control of Chronic and Emerging Infections (PCCEI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université des Antilles (UA)-Etablissement français du don du sang [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Boutin, Marion

Subjects
0301 basic medicine, Microbiology (medical), [SDV.BIO]Life Sciences [q-bio]/Biotechnology, viruses, 02 engineering and technology, Biology, Microbiology, Arbovirus, Dengue fever, 03 medical and health sciences, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, medicine, antibodies, lcsh:QH301-705.5, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Brief Report, RNA, virus diseases, magnetic agglutination, Amplicon, 021001 nanoscience & nanotechnology, medicine.disease, innovative diagnostic, 3. Good health, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, viral genomes, Agglutination (biology), 030104 developmental biology, arbovirus, lcsh:Biology (General), Biotinylation, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology.protein, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, nanoparticles, Turbidimetry, Antibody, 0210 nano-technology
Abstract

International audience; Arbovirus diagnostics on blood from donors and travelers returning from endemic areas is increasingly important for better patient management and epidemiological surveillance. We developed a flexible approach based on a magnetic field-enhanced agglutination (MFEA) readout to detect either genomes or host-derived antibodies. Dengue viruses (DENVs) were selected as models. For genome detection, a pan-flavivirus amplification was performed before capture of biotinylated amplicons between magnetic nanoparticles (MNPs) grafted with DENV probes and anti-biotin antibodies. Magnetization cycles accelerated this chaining process to within 5 min while simple turbidimetry measured the signal. This molecular MFEA readout was evaluated on 43 DENV RNA(+) and 32 DENV RNA(−) samples previously screened by real-time RT-PCR. The sensitivity and the specificity were 88.37% (95% CI, 78.76%–97.95%) and 96.87% (95% CI, 90.84%–100%), respectively. For anti-DENV antibody detection, 103 plasma samples from donors were first screened using ELISA assays. An immunological MFEA readout was then performed by adding MNPs grafted with viral antigens to the samples. Anti-DENV antibodies were detected with a sensitivity and specificity of 90.62% (95% CI, 83.50%–97.76%) and 97.44% (95% CI, 92.48%–100%), respectively. This adaptable approach offers flexibility to platforms dedicated to the screening of emerging infections

Published
2021
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3. Correlation between Bioassay and Protein Misfolding Cyclic Amplification for Variant Creutzfeldt-Jakob Disease Decontamination Studies

Author

Daisy Bougard, Vincent Béringue, Lilian Bruyère-Ostells, Maxime Belondrade, Laetitia Herzog, Fabienne Reine, Chantal Fournier-Wirth, Juan María Torres, Christelle Jas-Duval, Sylvain Lehmann, Charly Mayran, Simon Nicot, Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Université de Montpellier (UM), Virologie et Immunologie Moléculaires (VIM (UR 0892)), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centro de Investigacion en Sanidad Animal (INIA-CISA), Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria = National Institute for Agricultural and Food Research and Technology (INIA), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Boutin, Marion, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)

Subjects
0301 basic medicine, animal diseases, [SDV]Life Sciences [q-bio], Iatrogenic Disease, Population, lcsh:QR1-502, Mice, Transgenic, Microbiology, lcsh:Microbiology, Creutzfeldt-Jakob Syndrome, Prion Proteins, prion, Mice, 03 medical and health sciences, 0302 clinical medicine, PMCA, In vivo, Variant Creutzfeldt–Jakob disease, mental disorders, Animals, Humans, Medicine, Bioassay, Proteostasis Deficiencies, education, Molecular Biology, Infectivity, education.field_of_study, business.industry, Human decontamination, Therapeutics and Prevention, decontamination, variant Creutzfeldt-Jakob disease, Virology, QR1-502, In vitro, 3. Good health, nervous system diseases, [SDV] Life Sciences [q-bio], 030104 developmental biology, bioassay, Equipment Contamination, Protein Misfolding Cyclic Amplification, Female, business, 030217 neurology & neurosurgery, Research Article
Abstract

Creutzfeldt-Jakob diseases are neurodegenerative disorders for which transmission linked to medical procedures have been reported in hundreds of patients. As prion diseases, they are characterized by an unusual resistance to conventional decontamination processes. Moreover, their large tissue distribution and the ability of prions to attach to many surfaces raised the risk of transmission in health care facilities. It is therefore of major importance that decontamination procedures applied to medical devices before their reprocessing are thoroughly validated for prion inactivation. We previously described an in vitro assay, which allowed us to classify accurately prion decontamination treatments according to their efficacy on variant Creutzfeldt-Jakob disease. The significance of this study is in demonstrating the concordance between previous in vitro results and infectivity studies in transgenic mice. Furthermore, commercial reagents currently used in hospitals were tested by both protocols, and we observed that most of them were ineffective on human prions., To date, approximately 500 iatrogenic Creutzfeldt-Jakob disease cases have been reported worldwide, most of them resulting from cadaveric dura mater graft and from the administration of prion-contaminated human growth hormone. The unusual resistance of prions to decontamination processes, their large tissue distribution, and the uncertainty about the prevalence of variant Creutzfeldt-Jakob disease (vCJD) in the general population lead to specific recommendations regarding identification of tissue at risk and reprocessing of reusable medical devices, including the use of dedicated treatment for prion inactivation. We previously described an in vitro assay, called Surf-PMCA, which allowed us to classify prion decontamination treatments according to their efficacy on vCJD prions by monitoring residual seeding activity (RSA). Here, we used a transgenic mouse line permissive to vCJD prions to study the correlation between the RSA measured in vitro and the in vivo infectivity. Implantation in mouse brains of prion-contaminated steel wires subjected to different decontamination procedures allows us to demonstrate a good concordance between RSA measured by Surf-PMCA (in vitro) and residual infectivity (in vivo). These experiments emphasize the strength of the Surf-PMCA method as a rapid and sensitive assay for the evaluation of prion decontamination procedures and also confirm the lack of efficacy of several marketed reagents on vCJD prion decontamination. IMPORTANCE Creutzfeldt-Jakob diseases are neurodegenerative disorders for which transmission linked to medical procedures have been reported in hundreds of patients. As prion diseases, they are characterized by an unusual resistance to conventional decontamination processes. Moreover, their large tissue distribution and the ability of prions to attach to many surfaces raised the risk of transmission in health care facilities. It is therefore of major importance that decontamination procedures applied to medical devices before their reprocessing are thoroughly validated for prion inactivation. We previously described an in vitro assay, which allowed us to classify accurately prion decontamination treatments according to their efficacy on variant Creutzfeldt-Jakob disease. The significance of this study is in demonstrating the concordance between previous in vitro results and infectivity studies in transgenic mice. Furthermore, commercial reagents currently used in hospitals were tested by both protocols, and we observed that most of them were ineffective on human prions.

Published
2020
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4. An Innovative Multiplexed And Flexible Molecular Approach For The Differential Detection Of Arboviruses

Author

Jean-Charles Brès, Emilie Blanc, Albert Meyer, François Morvan, Robin Reynier, Philippe Van de Perre, Jean-François Cantaloube, Chantal Fournier-Wirth, Fanny Leon, Yannick Simonin, Lilian Bruyère-Ostells, Pierre Gallian, Jean-Jacques Vasseur, Isabelle Leparc-Goffart, Myrielle Dupont-Rouzeyrol, Sara Salinas, Vincent Foulongne, Antoine Biron, Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), 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), Dengue et Arbovirose (URE-DA), Institut Pasteur de Nouvelle-Calédonie, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Emergence des Pathologies Virales (EPV), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Établissement Français du Sang Alpes-Méditerranée (EFS Alpes-Méditerranée), Centre National de Référence (CNR) des Arbovirus - Laboratoire coordonnateur : Equipe Résidente de Recherche d'Infectiologie Tropicale (ERRIT), Institut de Recherche Biomédicale des Armées Hôpital d’Instruction des Armées Laveran, Supported by institutional funding from Etablissement Français du Sang (C.F.-W.) and Institut Pasteur de Nouvelle-Calédonie (M.D.-R.)., Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Etablissement français du don du sang [Montpellier], Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire Parole et Langage (LPL), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), EFS ALPES MEDITERRANEE, Etablissement Français du Sang [La Plaine Saint-Denis] (EFS), Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA), Centre National de Référence des Arbovirus [Marseille], Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA)-Unité d'Arbovirologie [Marseille], Hôpital d'Instruction des Armées Laveran, Service de Santé des Armées-Service de Santé des Armées-Hôpital d'Instruction des Armées Laveran, Service de Santé des Armées-Service de Santé des Armées, and Réseau International des Instituts Pasteur (RIIP)

Subjects
0301 basic medicine, viruses, Dengue virus, Biology, Nucleic Acid Testing, medicine.disease_cause, Genome, Sensitivity and Specificity, Virus, Pathology and Forensic Medicine, Zika virus, Dengue, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, Humans, Multiplex, Chikungunya, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Reverse Transcriptase Polymerase Chain Reaction, Zika Virus Infection, Nucleic Acid Hybridization, virus diseases, Zika Virus, Dengue Virus, biology.organism_classification, Virology, 3. Good health, Patient management, 030104 developmental biology, 030220 oncology & carcinogenesis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Molecular Medicine, Chikungunya Fever, Chikungunya virus, Multiplex Polymerase Chain Reaction
Abstract

International audience; Nucleic acid testing during the preseroconversion viremic phase is required to differentially diagnose arboviral infections. The continuing emergence of arboviruses, such as Zika virus (ZIKV), dengue virus (DENV), and chikungunya virus (CHIKV), necessitates the development of a flexible diagnostic approach. Similar clinical signs and the priority to protect pregnant women from ZIKV infection indicate that the differential diagnosis of arboviruses is essential for effective patient management, clinical care, and epidemiologic surveillance. We describe an innovative diagnostic approach that combines generic RT-PCR amplification and identification by hybridization to specific probes. Original tetrathiolated probes were designed for the robust, sensitive, and specific detection of amplified arboviral genomes. The limit of detection using cultured and quantified stocks of whole viruses was 1 TCID50/mL for DENV-1, DENV-3, and CHIKV and 10 TCID50/mL for DENV-2, DENV-4, and ZIKV. The assay had 100% specificity with no false-positive results. The approach was evaluated using 179 human samples that previously tested as positive for the presence of ZIKV, DENV, or CHIKV genomes. Accordingly, the diagnostic sensitivity for ZIKV, DENV, and CHIKV was 87.88% (n = 58/66), 96.67% (n = 58/60), and 94.34% (n = 50/53), respectively. This method could be easily adapted to include additional molecular targets. Moreover, this approach may also be adapted to develop highly specific, sensitive, and easy to handle platforms dedicated to the multiplex screening and identification of emerging viruses.

Published
2019
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5. Diagnosis of Methionine/Valine Variant Creutzfeldt-Jakob Disease by Protein Misfolding Cyclic Amplification

Author

Lilian Bruyère-Ostells, Chantal Fournier-Wirth, Maxime Belondrade, Robert G. Will, Sylvain Lehmann, Daisy Bougard, Alison Green, Charly Mayran, Richard Knight, Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Plateforme de Protéomique Clinique, CHU Saint-Eloi, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)

Subjects
diagnosis, Epidemiology, [SDV]Life Sciences [q-bio], animal diseases, lcsh:Medicine, Creutzfeldt-Jakob Syndrome, chemistry.chemical_compound, Methionine, 0302 clinical medicine, PMCA, protein misfolding cyclic amplification, Genotype, Variant Creutzfeldt–Jakob disease, 030212 general & internal medicine, Diagnosis of Methionine/Valine Variant Creutzfeldt-Jakob Disease by Protein Misfolding Cyclic Amplification, Dispatch, Valine, variant Creutzfeldt-Jakob disease, 3. Good health, Variant cjd, CJD, prions and related diseases, Infectious Diseases, Protein Misfolding Cyclic Amplification, genetic Creutzfeldt-Jakob disease, Microbiology (medical), sporadic Creutzfeldt-Jakob disease, CSF, Biology, Sensitivity and Specificity, Prion Proteins, cerebrospinal fluid, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, methionine/valine variant, mental disorders, Humans, vCJD, lcsh:RC109-216, Proteostasis Deficiencies, Gene, lcsh:R, Virology, Creutzfeldt-Jakob disease, nervous system diseases, chemistry, sCJD, gCJD, 030217 neurology & neurosurgery
Abstract

International audience; A patient with a heterozygous variant of Creutzfeldt-Jakob disease (CJD) with a methionine/valine genotype at codon 129 of the prion protein gene was recently reported. Using an ultrasensitive and specific protein misfolding cyclic amplification-based assay for detecting variant CJD prions in cerebrospinal fluid, we discriminated this heterozygous case of variant CJD from cases of sporadic CJD.

Published
2018
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6. Multiplex lateral flow assay for rapid visual blood group genotyping

Author

Francis Roubinet, Julien Gomez-Martinez, Chantal Fournier-Wirth, M. Silvy, P. Bailly, Jacques Chiaroni, Jean-Charles Brès, Etablissement français du sang [Pyrénées-Méditerranée] (EFS Pyrénées-Méditerranée), Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Etablissement Français du Sang - Alpes-Méditerranée (EFS - Alpes-Méditerranée), Etablissement Français du Sang, Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Université de Montpellier (UM)

Subjects
Genotype, Genotyping Techniques, Hemagglutination, [SDV]Life Sciences [q-bio], Single-nucleotide polymorphism, Computational biology, 030204 cardiovascular system & hematology, Polymorphism, Single Nucleotide, 01 natural sciences, Analytical Chemistry, 03 medical and health sciences, 0302 clinical medicine, Multiplex polymerase chain reaction, Humans, Multiplex, Genotyping, Alleles, Chemistry, 010401 analytical chemistry, DNA extraction, 3. Good health, 0104 chemical sciences, Blood Group Antigens, Multiplex Polymerase Chain Reaction
Abstract

International audience; Conventional blood group phenotyping by hemagglutination assays, carried out pretransfusion, is unsuitable in certain clinical situations. Molecular typing offers an alternative method, allowing the deduction of blood group phenotype from genotype. However, current methods require a long turnaround time and are not performed on-site, limiting their application in emergency situations. Here, we report the development of a novel, rapid multiplex molecular method to identify seven alleles in three clinically relevant blood group systems (Kidd, Duffy and MNS). Our test, using a dry-reagent allele-specific lateral flow biosensor, does not require DNA extraction and allows easy visual determination of blood group genotype. Multiplex linear-after-the-exponential (LATE)-PCR and lateral flow parameters were optimized with a total processing time of one hour from receiving the blood sample. Our assay had a 100 % concordance rate between the deduced and the standard serological phenotype in a sample from 108 blood donors, showing the accuracy of the test. Owing to its simple handling, the assay can be operated by non-skilled health-care professionals. The proposed assay offers the potential for the development of other relevant single nucleotide polymorphism (SNP) panels for immunohematology and new applications, such as for infectious diseases, in the near future.

Published
2018
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7. Transfusion sanguine : un modèle de questionnement en recherche et développement

Author

Joliette Coste, Chantal Fournier-Wirth, Pierre Tiberghien, Olivier Garraud, Pascal Morel, Université de Lyon, Institut National de la Transfusion Sanguine [Paris] (INTS), Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Laboratoire TransDiag-Sécurité Transfusionnelle et Innovation Diagnostique, Etablissement Français du Sang Pyrénées-Méditerranée, Etablissement Français du Sang [La Plaine Saint-Denis] (EFS), Pathogénèse et contrôle des infections chroniques (PCCI), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )

Subjects
Value (ethics), Blood transfusion, business.industry, medicine.medical_treatment, media_common.quotation_subject, MEDLINE, Translational medicine, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, General Medicine, 030204 cardiovascular system & hematology, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Transfusion reaction, Risk analysis (engineering), medicine, Production (economics), Quality (business), 030212 general & internal medicine, business, ComputingMilieux_MISCELLANEOUS, media_common
Abstract

Transfusion is a mixed discipline which includes the production of blood components, applied biology aiming in particular at establishing the highest compatibility for immunological characteristics between blood components to be delivered to patients and recipients, and, finally translational medicine to evaluate the effectiveness of the transfused products and to proactively avoid hazards, at least those that are preventible and can be anticipated. The whole chain takes place with the concern of continuous improvement of quality and safety. These two principles (quality/safety) have been and still are concerns of constant progress applicable to all the transfusion chain steps; they benefit from programs of Research and Development (R&D). Fundamental research, basic but also applied and clinical research, accompanies, in a constantly joint manner, scientific and medical progresses by providing new solutions to dampen the current problems and to prepare the future.

Published
2015
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8. Zika Virus Efficiently Replicates in Human Retinal Epithelium and Disturbs Its Permeability

Author

Krishna Damodar, Sara Salinas, Jean-Pierre Molès, Chantal Fournier-Wirth, Nejla Erkilic, Vasiliki Kalatzis, Yannick Simonin, Philippe Van de Perre, Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Université de Montpellier (UM), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Simonin, Yannick, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Institut des Neurosciences de Montpellier (INM), and CHU Montpellier

Subjects
0301 basic medicine, Microcephaly, [SDV]Life Sciences [q-bio], viruses, Immunology, Induced Pluripotent Stem Cells, polarized epithelia, Retinal Pigment Epithelium, Virus Replication, Microbiology, Asymptomatic, Retina, Permeability, Zika virus, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Virology, medicine, Animals, Humans, Author Correction, Letter to the Editor, ComputingMilieux_MISCELLANEOUS, biology, Zika Virus Infection, Retinal, Zika Virus, biology.organism_classification, medicine.disease, Epithelium, 3. Good health, [SDV] Life Sciences [q-bio], Flavivirus, 030104 developmental biology, medicine.anatomical_structure, chemistry, Insect Science, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 030221 ophthalmology & optometry, medicine.symptom, Biomarkers
Abstract

Recently, the flavivirus Zika virus (ZIKV) has rapidly spread in the Americas and the Caribbean islands. While a large proportion of infected persons are subjected to mild or asymptomatic disease, neurological disorders such as Guillain-Barre syndrome and microcephaly have been linked to ZIKV

Published
2016
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9. Le virus Zika L'émergence d'une menace

Author

Jean-Pierre Molès, Laurence Briant, Sara Salinas, Yannick Simonin, Vincent Foulongne, Chantal Fournier-Wirth, Philippe Van de Perre, Nicolas Nagot, Fabien Loustalot, Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Université de Montpellier (UM), Laboratoire de Virologie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire TransDiag, Etablissement Français du Sang, Institut de Recherche en Infectiologie de Montpellier (IRIM), and Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
myalgia, Pregnancy, Microcephaly, biology, business.industry, 030231 tropical medicine, Outbreak, General Medicine, biology.organism_classification, medicine.disease, Virology, Rash, Asymptomatic, General Biochemistry, Genetics and Molecular Biology, Virus, 3. Good health, Zika virus, 03 medical and health sciences, 0302 clinical medicine, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, medicine, 030212 general & internal medicine, medicine.symptom, business, ComputingMilieux_MISCELLANEOUS
Abstract

Zika virus, discovered in 1947, is particularly publicized because of its involvement in a major epidemic that began in 2015 and which epicenter is located in Latin America, mainly in Brazil. In the majority of cases (70-80 %) the infection is asymptomatic, however in some patients, moderate fever, skin rash, conjunctivitis and myalgia may occur. More alarming, neurological complications are reported, in particular cases of microcephaly probably resulting from the infection of women in the first or second trimester of pregnancy. Moreover, Guillain-Barre syndromes have also been identified in patients whose infection was confirmed. The extent of the current outbreak reveals the very primitive state of knowledge about the pathophysiology of this virus. Thus, a global effort is being undertaken in order to quickly characterize the molecular interaction of the virus with human cells, but also to develop specific diagnostic assays and vaccinal approaches.

Published
2016
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10. Detection of prions in the plasma of presymptomatic and symptomatic patients with variant Creutzfeldt-Jakob disease

Author

Joliette Coste, Christiane Segarra, Hervé Fleury, Maxime Belondrade, Stéphane Haïk, Jean-Philippe Brandel, Robert G. Will, Daisy Bougard, Simon Nicot, Jean-Louis Laplanche, Arlette Welaratne, Alison Green, David Narbey, Charly Mayran, Pierre Tiberghien, Richard Knight, Chantal Fournier-Wirth, Vincent Béringue, Pathogénèse et contrôle des infections chroniques (PCCI), Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Montpellier (UM), Etablissement Français du Sang, Cellule Nationale de Référence des Maladies de Creutzfeldt-Jakob, Hôpital Universitaire Pitié Salpêtrière, Assistance Publique - Hôpitaux de Paris (AP - HP), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), 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)-CHU Pitié-Salpêtrière [APHP], Centre National de la Recherche Scientifique (CNRS), Sorbonne Universités, Hôpital La Pitie Salpetriere, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Référence des Agents Transmissibles Non Conventionnels, Unité de recherche Virologie et Immunologie Moléculaires (VIM), Institut National de la Recherche Agronomique (INRA), Laboratoire de Virologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Service de Biochimie et Biologie Moléculaire, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière, National Creutzfeldt-Jakob Disease Research and Surveillance Unit, Centre for Clinical Brain Sciences, University of Edinburgh, UMR 1098 Interactions hôte-greffon-tumeur et ingénierie cellulaire et tissulaire., Université de Franche-Comté (UFC), Cellule Natl Reference Malad Creutzfeldt Jakob, Etablissement Francais du Sang, Alliance Biosecure Foundation (Prion Blood Confirm valid project), INSERM, Institut de Veille Sanitaire, program Investissements d'avenir [ANR-10-IAIHU-06], U.K. Department of Health Policy Research Programme [PRST061400008], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Université de Montpellier (UM), 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) (AP-HP), 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)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), 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), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)

Subjects
0301 basic medicine, Blood transfusion, Bovine spongiform encephalopathy, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Population, Disease, Sensitivity and Specificity, Creutzfeldt-Jakob Syndrome, Prion Proteins, 03 medical and health sciences, 0302 clinical medicine, Variant Creutzfeldt–Jakob disease, mental disorders, medicine, Humans, education, education.field_of_study, Hematologic Tests, Transmission (medicine), business.industry, Reproducibility of Results, General Medicine, medicine.disease, Virology, United Kingdom, 3. Good health, nervous system diseases, 030104 developmental biology, Treatment Outcome, Protein Misfolding Cyclic Amplification, France, business, Asymptomatic carrier, 030217 neurology & neurosurgery
Abstract

Variant Creutzfeldt-Jakob disease (vCJD) is a human prion disease resulting from the consumption of meat products contaminated by the agent causing bovine spongiform encephalopathy. Evidence supporting the presence of a population of silent carriers that can potentially transmit the disease through blood transfusion is increasing. The development of a blood-screening assay for both symptomatic vCJD patients and asymptomatic carriers is urgently required. We show that a diagnostic assay combining plasminogen-bead capture and protein misfolding cyclic amplification (PMCA) technologies consistently detected minute amounts of abnormal prion protein from French and British vCJD cases in the required femtomolar range. This assay allowed the blinded identification of 18 patients with clinical vCJD among 256 plasma samples from the two most affected countries, with 100% sensitivity [95% confidence interval (CI), 81.5 to 100%], 99.2% analytical specificity (95% CI, 95.9 to 100%), and 100% diagnostic specificity (95% CI, 96.5 to 100%). This assay also allowed the detection of silent carriage of prions 1.3 and 2.6 years before the clinical onset in two blood donors who later developed vCJD. These data provide a key step toward the validation of this PMCA technology as a blood-based diagnostic test for vCJD and support its potential for detecting presymptomatic patients, a prerequisite for limiting the risk of vCJD transmission through blood transfusion.

Published
2016
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11. Microconductometric immunosensor for label-free and sensitive detection of Gram-negative bacteria

Author

Ludivine Vossier, Sarra El Ichi, Hélène Marchandin, Nicole Jaffrezic-Renault, Abdelhamid Errachid, Joliette Coste, Chantal Fournier-Wirth, Fanny Leon, Laboratoire TransDiag, Etablissement Français du Sang, SIMS - Surfaces-(bio)Interfaces - Micro & Nano Systèmes (2011-2014), Institut des Sciences Analytiques (ISA), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Ecologie des systèmes marins côtiers (Ecosym), and Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Gram-negative bacteria, Conductometry, Biomedical Engineering, Biophysics, 02 engineering and technology, Biosensing Techniques, medicine.disease_cause, 01 natural sciences, Microbiology, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Limit of Detection, Gram-Negative Bacteria, Electrochemistry, medicine, Humans, Magnetite Nanoparticles, Escherichia coli, Immunoassay, biology, Pseudomonas aeruginosa, 010401 analytical chemistry, General Medicine, 021001 nanoscience & nanotechnology, biology.organism_classification, 3. Good health, 0104 chemical sciences, Acinetobacter baumannii, Serratia marcescens, biology.protein, Antibody, 0210 nano-technology, Gram-Negative Bacterial Infections, Biosensor, Antibodies, Immobilized, Bacteria, Biotechnology
Abstract

International audience; : Blood safety is a global health goal. In developed countries, bacterial contamination of platelet concentrates is the highest infectious risk in transfusion despite the current preventive strategies. We aimed to develop a conductometric biosensor for the generic, rapid and sensitive detection of Gram-negative bacteria. Our strategy is based on immunosensors: addressable magnetic nanoparticles coupled with anti-LPS antibodies were used for the generic capture of Gram-negative bacteria. Bacterial capture was characterized by impedancemetric and microscopic measurements. The results obtained with conductometric measurements allowed real-time, sensitive detection of Escherichia coli or Serratia marcescens cultures from 1 to 10(3)CFUmL(-1). The ability of the immunosensor to detect Gram negative bacteria was also tested on clinically relevant strains. The conductometric immunosensor allowed the direct detection of 10-10(3)CFUmL(-1) of Pseudomonas aeruginosa and Acinetobacter baumannii strains that were undetectable using standard immunoblot methods. Results showed that the conductometric response was not inhibited in 1% serum.

Published
2013
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12. Identification of apolipoprotein C-III as a potential plasmatic biomarker associated with the resolution of hepatitis C virus infection

Author

Chantal Fournier-Wirth, Stéphanie Badiou, Claude Bonfils, Patrick Maurel, Thierry Levayer, Stéphane Roche, Jean-Paul Cristol, Dorothée Missé, Francisco Veas, Dominique Bonnefont-Rousselot, Jean-François Dierick, Sonia Molina, Joliette Coste, Physiopathologie hépatique, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Plateforme de Protéomique Clinique, CHU Saint-Eloi, Génotypes et phénotypes tumoraux, CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Biochimie Métabolique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire TransDiag, Etablissement Français du Sang, Roche, Stephane, Génétique et évolution des maladies infectieuses (GEMI), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
[SDV.BIO]Life Sciences [q-bio]/Biotechnology, Apolipoprotein B, Hepatitis C virus, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Clinical Biochemistry, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Biology, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, medicine.disease_cause, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Virus, HCV clearance, 03 medical and health sciences, Plasma, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, ApoC III, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Seroconversion, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], SELDI TOF MS, plasma, 030304 developmental biology, 0303 health sciences, SELDI-TOF, Apolipoprotein C-III, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Biomarker, Virology, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, ApoC-III, Chronic infection, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, 030220 oncology & carcinogenesis, Immunology, biology.protein, Biomarker (medicine), [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], biomarker, Viral disease
Abstract

International audience; Understanding the virus-host interactions that lead to approximately 20% of patients with acute Hepatitis C Virus (HCV) infection to viral clearance is probably a key towards the development of more effective treatment and prevention strategies. Acute hepatitis C infection is usually asymptomatic and therefore rarely diagnosed. Nevertheless, HCV nucleic acid testing carried out on all blood donations detects donors who have resolved their HCV infection after seroconver-sion. Here we have used SELDI-TOF-MS technology to compare, at a proteomic level, plasma samples respectively from donors with HCV clearance, from donors with chronic HCV infection and from unexposed healthy donors (n = 15 per group). A candidate marker of about 9.4 kDa was detected as differentially expressed in the three groups. After purification we identified by nanoLC-Q-TOF-MS/MS this candidate marker as Apolipoprotein C-III (ApoC-III). The identification was confirmed by western blot analysis. Levels of ApoC-III were then determined in the 45 plasma samples by immunoturbidimetric assay. ApoC-III was found to be higher in donors who had resolved their HCV infection than in donors with chronic infection, results which were consistent with SELDI-TOF-MS data. ApoC-III is the first reported candidate biomarker in plasma associated with the spontaneous resolution of HCV infection.

Published
2008
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13. Serum-derived hepatitis C virus infection of primary human hepatocytes is tetraspanin CD81 dependent

Author

Patrick Maurel, Chantal Fournier-Wirth, Valerie Castet, Czeslaw Wychowski, Jane A. McKeating, Antonio Sa-Cunha, Jean-Michel Fabre, Eliane F. Meurs, Joliette Coste, Dominique Larrey, Jean Dubuisson, Lydiane Pichard-Garcia, Jean-Marc Pascussi, Camille Sureau, and Sonia Molina

Subjects
Adult, Male, Virus genetics, Adolescent, Hepatitis C virus, Hepacivirus, viruses, Immunology, medicine.disease_cause, Microbiology, Tetraspanin 28, 03 medical and health sciences, 0302 clinical medicine, Antigens, CD, Virology, medicine, Humans, Gene Silencing, Cells, Cultured, 030304 developmental biology, Aged, 0303 health sciences, biology, Hepatitis C, biochemical phenomena, metabolism, and nutrition, Middle Aged, Virus Internalization, medicine.disease, biology.organism_classification, 3. Good health, Virus-Cell Interactions, Cell culture, Insect Science, biology.protein, Hepatocytes, RNA, Viral, Receptors, Virus, 030211 gastroenterology & hepatology, Female, Antibody, Viral load, CD81
Abstract

Hepatitis C virus-positive serum (HCVser, genotypes 1a to 3a) or HCV cell culture (JFH1/HCVcc) infection of primary normal human hepatocytes was assessed by measuring intracellular HCV RNA strands. Anti-CD81 antibodies and siRNA-CD81 silencing markedly inhibited (>90%) HCVser infection irrespective of HCV genotype, viral load, or liver donor, while hCD81-large intracellular loop (LEL) had no effect. However, JFH1/HCVcc infection of hepatocytes was modestly inhibited (40 to 60%) by both hCD81-LEL and anti-CD81 antibodies. In conclusion, CD81 is involved in HCVser infection of human hepatocytes, and comparative studies of HCVser versus JFH1/HCVcc infection of human hepatocytes and Huh-7.5 cells revealed that the cell-virion combination is determinant of the entry process.

Published
2007

14. The low-density lipoprotein receptor plays a role in the infection of primary human hepatocytes by hepatitis C virus

Author

Dror Harats, Paola Ghersa, Valérie Castet, Moshe Smolarsky, Dominique Larrey, Ronald Barbaras, Joliette Coste, Patrick Maurel, Fabio Malavasi, Antonio Sa-Cunha, Jean-Michel Fabre, Joseph Roitelman, Sonia Molina, Lydiane Pichard-Garcia, Ada Funaro, Rachel Avner, Pierre Graber, Chantal Fournier-Wirth, Physiopathologie hépatique, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM), EFS, Etablissement Français du Sang, Institute of Lipid and Atherosclerosis Research, Sheba Medical Center, 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), Serono SPRI, Serono InterPharm, Università degli studi di Torino (UNITO), Service d'Hépatogastroentérologie, CHU Saint-Eloi, Service de Chirurgie Digestive II, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Service de Chirurgie Digestive, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux], Maurel, Patrick, Università degli studi di Torino = University of Turin (UNITO), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)

Subjects
Male, MESH: Lipoproteins, LDL, Hepacivirus, medicine.disease_cause, MESH: Lipoproteins, HDL, MESH: Bicyclo Compounds, Heterocyclic, MESH: Hepatocytes, Virus entry, chemistry.chemical_compound, MESH: Hydroxycholesterols, 0302 clinical medicine, MESH: Hepacivirus, Cells, Cultured, MESH: Aged, MESH: Antigens, CD18, 0303 health sciences, MESH: Middle Aged, Anticholesteremic Agents, Virus receptor, Genome replication, Middle Aged, Scavenger Receptors, Class B, Viral Load, Hepatitis C, MESH: Gene Expression Regulation, 3. Good health, Lipoproteins, LDL, Low-density lipoprotein, MESH: RNA, Viral, RNA, Viral, MESH: Virion, Female, 030211 gastroenterology & hepatology, lipids (amino acids, peptides, and proteins), Lipoproteins, HDL, MESH: Viral Load, Viral load, MESH: Cells, Cultured, Adult, Adolescent, Hepatitis C virus, Biology, MESH: Anticholesteremic Agents, Antibodies, 03 medical and health sciences, Viral entry, medicine, Humans, Scavenger receptor, Aged, 030304 developmental biology, MESH: Adolescent, MESH: Hepatitis C, MESH: Humans, Hepatology, MESH: Antibodies, Virion, Tricarboxylic Acids, MESH: Adult, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Bridged Bicyclo Compounds, Heterocyclic, Virology, Hydroxycholesterols, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH: Male, MESH: Scavenger Receptors, Class B, Gene Expression Regulation, Receptors, LDL, chemistry, MESH: Receptors, LDL, MESH: Tricarboxylic Acids, CD18 Antigens, LDL receptor, Hepatocytes, MESH: Female, Lipoprotein
Abstract

International audience; BACKGROUND/AIMS: The direct implication of low-density lipoprotein receptor (LDLR) in hepatitis C virus (HCV) infection of human hepatocyte has not been demonstrated. Normal primary human hepatocytes infected by serum HCV were used to document this point. METHODS: Expression and activity of LDLR were assessed by RT-PCR and LDL entry, in the absence or presence of squalestatin or 25-hydroxycholesterol that up- or down-regulates LDLR expression, respectively. Infection was performed in the absence or presence of LDL, HDL, recombinant soluble LDLR peptides encompassing full-length (r-shLDLR4-292) or truncated (r-shLDLR4-166) LDL-binding domain, monoclonal antibodies against r-shLDLR4-292, squalestatin or 25-hydroxycholesterol. Intracellular amounts of replicative and genomic HCV RNA strands used as end point of infection were assessed by RT-PCR. RESULTS: r-shLDLR4-292, antibodies against r-shLDLR4-292 and LDL inhibited viral RNA accumulation, irrespective of genotype, viral load or liver donor. Inhibition was greatest when r-shLDLR4-292 was present at the time of inoculation and gradually decreased as the delay between inoculation and r-shLDLR4-292 treatment increased. In hepatocytes pre-treated with squalestatin or 25-hydroxycholesterol before infection, viral RNA accumulation increased or decreased in parallel with LDLR mRNA expression and LDL entry. CONCLUSIONS: LDLR is involved at an early stage in infection of normal human hepatocytes by serum-derived HCV virions.

Published
2007
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15. Zika Virus Strains Potentially Display Different Infectious Profiles in Human Neural Cells

Author

Jean-Marc Lemaitre, Fanny Leon, Marianne Maquart, Jean-Pierre Molès, Orianne Constant, Aurélien Goubaud, Yannick Simonin, Chantal Fournier-Wirth, Nicolas Nagot, Caroline Desmetz, Laurence Briant, Philippe Van de Perre, Fabien Loustalot, Sara Salinas, Vincent Foulongne, Isabelle Leparc-Goffart, Pathogénèse et contrôle des infections chroniques (PCCI), Université de Montpellier ( UM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre Hospitalier Universitaire de Montpellier ( CHU Montpellier ), Agroécologie [Dijon], Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Laboratoire de Virologie, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Thales Services, THALES, Laboratoire TransDiag, Etablissement Français du Sang, Instituto de Productos Naturales y Agrobiologia-C.S.I.C.-Instituto Universitario de Bio-Organica ‘‘Antonio Gonzalez,’’ Universidad de La Laguna, CHU de Montpellier, Centre de Coopération Internationale en Recherche Agronomique pour le Développement ( CIRAD ), French National Reference Centre for Arboviruses, IRBA Armed Forces Biomedical Research Institute, Institut de Recherche en Infectiologie de Montpellier ( IRIM ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Montpellier ( UM ), Medical Informatics Department, University Hospital, 39 Avenue Charles Flahault, 34090 Montpellier cedex 5, Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique Moléculaire de Montpellier (IGMM), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)

Subjects
0301 basic medicine, Lineage (genetic), Cell Survival, 030106 microbiology, lcsh:Medicine, Neuropathology, Virus Replication, [ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, General Biochemistry, Genetics and Molecular Biology, Virus, Zika virus, 03 medical and health sciences, Animals, Humans, Lineages, Vero Cells, ComputingMilieux_MISCELLANEOUS, Phylogeny, Infectivity, Neural stem cells, lcsh:R5-920, biology, Zika Virus Infection, Strain (biology), lcsh:R, Outbreak, General Medicine, biology.organism_classification, Virology, Neural stem cell, 3. Good health, Viral Tropism, 030104 developmental biology, Astrocytes, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, lcsh:Medicine (General), Research Paper
Abstract

The recent Zika virus (ZIKV) epidemic has highlighted the poor knowledge on its physiopathology. Recent studies showed that ZIKV of the Asian lineage, responsible for this international outbreak, causes neuropathology in vitro and in vivo. However, two African lineages exist and the virus is currently found circulating in Africa. The original African strain was also suggested to be neurovirulent but its laboratory usage has been criticized due to its multiple passages. In this study, we compared the French Polynesian (Asian) ZIKV strain to an African strain isolated in Central African Republic and show a difference in infectivity and cellular response between both strains in human neural stem cells and astrocytes. Consistently, this African strain led to a higher infection rate and viral production, as well as stronger cell death and anti-viral response. Our results highlight the need to better characterize the physiopathology and predict neurological impairment associated with African ZIKV., Highlights • ZIKV from two Asian and African strains infect differentially IPSc-derived NSCs • African ZIKV strain displays more infectivity and anti-viral response • African and Asian ZIKV strains infect and replicate efficiently in human astrocytes Zika virus (ZIKV) is involved in a major epidemic in Latin America. Some neurological complications are reported following infection, in particular microcephaly and Guillain-Barré syndromes. Analyses show that one Asian and two Africans lineages exist. Although originally discovered in Africa in 1947, the actual epidemic is due to Asian ZIKV. Here, we compared the virulence of two African and Asian ZIKV strains in neural cells. We showed that in human neural stem cells, African ZIKV strain had a higher infectivity and triggered stronger cellular response. Altogether, our results highlight the need to better characterize ZIKV lineages to anticipate further epidemics.

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