Search

Your search keyword '"Erika Hue"' showing total 33 results
Start Over Author "Erika Hue" Language english
33 results on '"Erika Hue"'

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

Author

Côme Thieulent, Christine Fortier, Hélène Munier-Lehmann, Peggy Suzanne, Patrick Dallemagne, Stephan Zientara, Aymeric Hans, Romain Paillot, Pierre-Olivier Vidalain, Stéphane Pronost, and Erika Hue

Subjects
Real-time cell assay, Chemical library screening, Antiviral, Equid herpesvirus-1, Computer applications to medicine. Medical informatics, R858-859.7, Science (General), Q1-390
Abstract

Data presented in this article are associated with the research article “Identification of antiviral compounds against equid herpesvirus-1 using real-time cell assay screening: efficacy of decitabine and valganciclovir alone and in combination” [1]. These data correspond to the in vitro screening of 2,891 potential antiviral compounds against equid herpesvirus-1 (EHV-1) based on impedance measurements using the xCELLigence® RTCA MP System. This dataset includes compounds from three different libraries: i) 1,199 compounds from the Prestwick® Chemical Library, which contains mostly US Food and Drug Administration approved drugs (Prestwick® Chemical, Illkirch, France); ii) 1,651 compounds from the Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN, Caen, France); iii) 41 compounds (called herein in-house antiviral library) selected for their effects against different human viruses. Compounds effective against EHV-1 were selected using the area under normalised curves (AUCn) and the time required for the Cell Index to decrease by 50% after virus infection (CIT50). The full dataset from the screen is made publicly available for further analyses.

Published
2020
Full Text
View/download PDF

2. Asymmetrical Pulmonary Cytokine Profiles Are Linked to Bronchoalveolar Lavage Fluid Cytology of Horses With Mild Airway Neutrophilia

Author

Erika Hue, Marie Orard, Marie-Pierre Toquet, Marianne Depecker, Anne Couroucé, Stéphane Pronost, Romain Paillot, and Eric A. Richard

Subjects
horse, equine asthma, bronchoalveolar lavage fluid, neutrophils, IL-10, IL-1β, Veterinary medicine, SF600-1100
Abstract

Few data on cytokine profiles in bronchoalveolar lavage fluid (BALF) are available for racehorses with mild/moderate equine asthma (EA); cytological diagnosis being most frequently made from only one lung. The purpose of the study was to compare cytokine mRNA expressions and protein concentrations in BALF from both lungs. As part of a larger study, 250 ml saline was randomly instilled in one lung and 500 ml in the contralateral lung of 30 clinically healthy Standardbred racehorses. This procedure was repeated 72 h later, inversing the volume per lung. Cytological cut-off values for diagnosis of mild EA was neutrophil proportions > 10% when instilling 250 ml. Eleven horses that exhibited unilateral mild inflammatory cytology [i.e., normal cytology (

Published
2020
Full Text
View/download PDF

3. Oral Administration of Valganciclovir Reduces Clinical Signs, Virus Shedding and Cell-Associated Viremia in Ponies Experimentally Infected with the Equid Herpesvirus-1 C2254 Variant

Author

Côme J. Thieulent, Gabrielle Sutton, Marie-Pierre Toquet, Samuel Fremaux, Erika Hue, Christine Fortier, Alexis Pléau, Alain Deslis, Stéphane Abrioux, Edouard Guitton, Stéphane Pronost, and Romain Paillot

Subjects
valganciclovir, ganciclovir, EHV-1, equid alphaherpesvirus-1, herpesvirus, antiviral, Medicine
Abstract

Equid alphaherpesvirus-1 (EHV-1) is one of the main pathogens in horses, responsible for respiratory diseases, ocular diseases, abortions, neonatal foal death and neurological complications such as equine herpesvirus myeloencephalopathy (EHM). Current vaccines reduce the excretion and dissemination of the virus and, therefore, the extent of an epizooty. While their efficacy against EHV-1-induced abortion in pregnant mares and the decreased occurrence of an abortion storm in the field have been reported, their potential efficacy against the neurological form of disease remains undocumented. No antiviral treatment against EHV-1 is marketed and recommended to date. This study aimed to measure the protection induced by valganciclovir (VGCV), the prodrug of ganciclovir, in Welsh mountain ponies experimentally infected with an EHV-1 ORF30-C2254 strain. Four ponies were administered VGCV immediately prior to experimental EHV-1 infection, while another four ponies received a placebo. The treatment consisted in 6.5 mg/kg body weight of valganciclovir administered orally three times the first day and twice daily for 13 days. Clinical signs of disease, virus shedding and viraemia were measured for up to 3 weeks. The severity of the cumulative clinical score was significantly reduced in the treated group when compared with the control group. Shedding of infectious EHV-1 was significantly reduced in the treated group when compared with the control group between Day + 1 (D + 1) and D + 12. Viraemia was significantly reduced in the treated group when compared with the control group. Seroconversion was measured in all the ponies included in the study, irrespective of the treatment received. Oral administration of valganciclovir induced no noticeable side effect but reduced clinical signs of disease, infectious virus shedding and viraemia in ponies experimentally infected with the EHV-1 C2254 variant.

Published
2022
Full Text
View/download PDF

4. The influence of hay steaming on clinical signs and airway immune response in severe asthmatic horses

Author

Marie Orard, Erika Hue, Anne Couroucé, Céline Bizon-Mercier, Marie-Pierre Toquet, Meriel Moore-Colyer, Laurent Couëtil, Stéphane Pronost, Romain Paillot, Magali Demoor, and Eric A. Richard

Subjects
Equine asthma, Hay steaming, Inflammation, Cytology, Cytokines, Veterinary medicine, SF600-1100
Abstract

Abstract Background Avoidance of antigenic stimuli was found to significantly reverse airway obstruction of horses with severe equine asthma (sEA). To date, no published study investigated the influence of steaming hay on lower airway condition of sEA-affected horses. The objectives were to determine the clinical, cytological and cytokine respiratory responses of both sEA and control (CTL) horses experimentally exposed to steamed or dry hay. Results A cohort of 6 sEA horses and 6 CTL horses was involved in this field study. On day 0, both groups were fed with steamed hay for 5 consecutive days, followed by a wash-out period of 26 days prior to be fed with dry hay for 5 consecutive days. Investigations performed 2 days prior to and 5 days after each challenge included clinical score, tracheal mucus accumulation, and bronchoalveolar lavage fluid (BALF) cytology and cytokine mRNA expression. Feeding steamed hay significantly decreased its mould content (P

Published
2018
Full Text
View/download PDF

5. Porcine Reproductive and Respiratory Syndrome Virus Interferes with Swine Influenza A Virus Infection of Epithelial Cells

Author

Georges Saade, Déborah Ménard, Caroline Hervet, Patricia Renson, Erika Hue, Jianzhong Zhu, Laurence Dubreil, Romain Paillot, Stéphane Pronost, Olivier Bourry, Gaëlle Simon, Joëlle Dupont, Nicolas Bertho, and François Meurens

Subjects
pig, PRRSV, swIAV, coinfection, epithelial cell, interference, Medicine
Abstract

Respiratory infections are still a major concern in pigs. Amongst the involved viruses, the porcine reproductive and respiratory syndrome virus (PRRSV) and the swine influenza type A virus (swIAV) have a major impact. These viruses frequently encounter and dual infections are reported. We analyzed here the molecular interactions between viruses and porcine tracheal epithelial cells as well as lung tissue. PRRSV-1 species do not infect porcine respiratory epithelial cells. However, PRRSV-1, when inoculated simultaneously or shortly before swIAV, was able to inhibit swIAV H1N2 infection, modulate the interferon response and alter signaling protein phosphorylations (ERK, AKT, AMPK, and JAK2), in our conditions. SwIAV inhibition was also observed, although at a lower level, by inactivated PRRSV-1, whereas acid wash treatment inactivating non-penetrated viruses suppressed the interference effect. PRRSV-1 and swIAV may interact at several stages, before their attachment to the cells, when they attach to their receptors, and later on. In conclusion, we showed for the first time that PRRSV can alter the relation between swIAV and its main target cells, opening the doors to further studies on the interplay between viruses. Consequences of these peculiar interactions on viral infections and vaccinations using modified live vaccines require further investigations.

Published
2020
Full Text
View/download PDF

6. Distinct roles of Bcl-2 and Bcl-Xl in the apoptosis of human bone marrow mesenchymal stem cells during differentiation.

Author

Lisa Oliver, Erika Hue, Julien Rossignol, Gwenola Bougras, Philippe Hulin, Philippe Naveilhan, Dominique Heymann, Laurent Lescaudron, and François M Vallette

Subjects
Medicine, Science
Abstract

BackgroundAdult mesenchymal stem cells (MSCs) can be maintained over extended periods of time before activation and differentiation. Little is known about the programs that sustain the survival of these cells.Principal findingsUndifferentiated adult human MSCs (hMSCs) did not undergo apoptosis in response to different cell death inducers. Conversely, the same inducers can readily induce apoptosis when hMSCs are engaged in the early stages of differentiation. The survival of undifferentiated cells is linked to the expression of Bcl-Xl and Bcl-2 in completely opposite ways. Bcl-Xl is expressed at similar levels in undifferentiated and differentiated hMSCs while Bcl-2 is expressed only in differentiated cells. In undifferentiated hMSCs, the down-regulation of Bcl-Xl is associated with an increased sensitivity to apoptosis while the ectopic expression of Bcl-2 induced apoptosis. This apoptosis is linked to the presence of cytoplasmic Nur 77 in undifferentiated hMSCs.SignificanceIn hMSCs, the expression of Bcl-2 depends on cellular differentiation and can be either pro- or anti-apoptotic. Bcl-Xl, on the other hand, exhibits an anti-apoptotic activity under all conditions.

Published
2011
Full Text
View/download PDF

7. Differential dependence on Beclin 1 for the regulation of pro-survival autophagy by Bcl-2 and Bcl-xL in HCT116 colorectal cancer cells.

Author

Muriel Priault, Erika Hue, Fanny Marhuenda, Paul Pilet, Lisa Oliver, and François M Vallette

Subjects
Medicine, Science
Abstract

Autophagy is described to be involved in homeostasis, development and disease, both as a survival and a death process. Its involvement in cell death proceeds from interrelationships with the apoptotic pathway. We focused on survival autophagy and investigated its interplays with the apoptotic machinery. We found that while Mcl-1 remained ineffective, Bcl-2 and Bcl-xL were required for starved cells to display a fully functional autophagic pathway as shown by proteolysis activity and detection of autophagic vesicles. Such pro-autophagic functions of Bcl-2 and Bcl-xL were independent of Bax. However they appeared to operate through non redundant mechanisms as Bcl-xL wielded a tighter control than Bcl-2 over the regulation of autophagy: unlike Bcl-2, Bcl-xL and Atg7 manipulation yielded identical phenotypes suggesting they could be components of the same signalling pathway; Bcl-xL subcellular localisation was modified upon starvation, and importantly Bcl-xL acted independently of Beclin 1. Still an intact BH3-binding site was required for Bcl-xL to stimulate a fully functional autophagic pathway. This study highlights that, in addition to their well-established anti-death function during apoptosis, Bcl-2 and Bcl-xL have a broader role in cell survival. Should Bcl-2 and Bcl-xL stand at the cross-roads between pro-survival and pro-death autophagy, this study introduces the new concept that the regulation of autophagy by Bcl-2 and Bcl-xL is adjusted according to its survival or death outcome.

Published
2010
Full Text
View/download PDF

8. Investigating the interest of proton therapy to obtund radiation-induced lymphopenia in a context of brain tumour irradiation: a preclinical study

Author

Julie Coupey, Jérôme Toutain, Erika HUE, Hélaine, C., Jade Richard, Romaric Saulnier, Chazalviel Laurent, Marc Rousseau, Juliette Thariat, Valable Samuel, Leblond, M. M., Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), LABÉO, Pôle d’analyses et de recherche de Normandie (LABÉO), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Normandie Université (NU)-Normandie Université (NU), Unité Support CYCERON, Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre National de la Recherche Scientifique (CNRS), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de physique corpusculaire de Caen (LPCC), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Normandie Université (NU)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), and HUE, Erika

Subjects
brain radiotherapy, [SDV.CAN] Life Sciences [q-bio]/Cancer, proton therapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, lymphopenia
Abstract

CERVOXY; International audience; Although conventional radiotherapy based on X-rays improves brain tumour patient survival, it also leads to deleterious effects on the inflammatory component: enrichment of pro-tumour macrophages1 as well as recruitment of myeloid cells at the tumour site and severe lymphopenia2. This radiation-induced lymphopenia and enrichment in protumoral macrophages in the tumour bulk could decrease the immunotherapeutic response and are associated to a poor prognosis3. Proton therapy has emerged as a new radiation strategy for brain tumours. Thanks to its precise dose deposition, it enables to spare healthy tissue and circulating leukocytes4, and to its different biological effects on the irradiated tissue5, it could result in less harmful effects for systemic inflammation6. In this project, we aim to evaluate if brain radiation with proton therapy is less deleterious for circulating leukocytes than conventional brain radiotherapy.Tumour-free mice have been irradiated with X-rays (X-Rad 225 Cx GIP CYCERON, Caen) or proton beams (25MeV PRECy platform, Strasbourg). For each type of radiation, mice were divided according to radiation volume (whole-brain or hemisphere). Mice were irradiated twice a day (2.5 Gy/session) for four consecutive days. Blood samples were collected before, during and after radiation and circulating leukocytes were analysed by flow cytometry. First experiments confirmed the feasibility of the protocol.Preliminary data showed that mice weight decreased after whole-brain radiation with X-rays but not with proton beams. Blood sampling confirmed radiation-induced lymphopenia after irradiation with X-Rays, wholebrain irradiation inducing a more pronounced effect than hemisphere irradiation. Changes in leukocytes after proton-irradiation are under investigation but preliminary results suggest a conservative effect on leukocytes. Proton therapy appears as a better radiotherapy option for brain tumour but its effects on inflammation remains to be further analysed.

Published
2021

9. Hepatitis viruses: prevalence of equine parvovirus-hepatitis virus and equine hepacivirus in France and Australia

Author

N. J. Bamford, Gabrielle Sutton, Christine Fortier, Erika Hue, K. Jeffers, Stéphane Pronost, Romain Paillot, Carol A. Hartley, James R. Gilkerson, Charlie El-Hage, Christel Marcillaud Pitel, Elise Oden, LABÉO, Pôle d’analyses et de recherche de Normandie (LABÉO), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), University of Melbourne, Réseau d'Epidémio-Surveillance en Pathologie Équine (RESPE), School of Equine and Veterinary Physiotherapy, and Writtle University College (WUC)

Subjects
Hepatitis virus, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, Phylogenetic tree, biology, 040301 veterinary sciences, Parvovirus, 0402 animal and dairy science, 04 agricultural and veterinary sciences, General Medicine, biology.organism_classification, 040201 dairy & animal science, Virology, Genome, 3. Good health, 0403 veterinary science, chemistry.chemical_compound, chemistry, Population study, Equine hepacivirus, Viral load, NS5B
Abstract

Background: Recent identification of viruses considered responsible for Theiler’s disease (acute hepatitis) in horses include equine parvovirus-hepatitis (EqPV-H) and the most likely of several flaviviruses, equine hepacivirus (EqHV). Both of these viruses have now been detected in North America, Asia, and Europe. Objectives: To determine the prevalence of EqPV-H and EqHV in French and Australian horses and to analyse their respective phylogenetic relationships. Study design: Cross-sectional. Methods: Clinically documented sera from 188 Australian horses and 259 French horses collected between 2016-2019 were analysed. qPCRs validated according to the NF47-600 standard were used to detect EqPV-H and EqHV in sera. Sequencing for phylogenetic analysis was performed on two NS1 fragments (516 nt and 587 nt) for EqPV-H and one NS5B fragment (308 nt) for EqHV. A phylogenic network was built using a Median Joining Network algorithm. Results: 1) EqPV-H: 12/259 (4.6%) and 6/188 (3.2%) samples from French and Australian horses were positive, respectively. Viral loads ranged from 2.3e05 to 6.5e05 copies genome/ml. 2) EqHV: 5/259 (1.9%) and 21/188 (11.2%) samples from French and Australian horses were positive, respectively. Viral loads ranged from 6.1e04 to 1.4e08 copies genome/ml. Both EqPV-H (587 nt fragment) and EqHV phylogenetic analyses showed that Australian strains were clustered, while overall distribution was more heterogenous in French horses. Main limitations: The study population is built by accessing laboratory submissions and potentially biased. The 516 nt NS1 fragment could not be sequenced. Conclusions: This is the first report of EqPV-H detection in both Australian and French horses. The EqPV-H prevalence was similar between the two countries (p-value=0.6) although phylogenetic differences were observed between the two populations. This is also the first reported detection of EqHV in Australian horses, with a higher prevalence when compared with French horses.

Published
2021
Full Text
View/download PDF

10. Circulation and characterisation of Equid herpesvirus-3 strains in France between 2010 and 2021

Author

Christine Fortier, Erika Hue, Côme Thieulent, Loïc Legrand, Christel Marcillaud Pitel, Stéphane Pronost, Camille Normand, Gabrielle Sutton, LABÉO, Pôle d’analyses et de recherche de Normandie (LABÉO), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Réseau d'Epidémio-Surveillance en Pathologie Équine (RESPE), HUE, Erika, and ImpedanCELL

Subjects
Ganciclovir, Aphidicolin, 040301 veterinary sciences, Biology, EHV-3, 0403 veterinary science, chemistry.chemical_compound, medicine, Aciclovir, Vidarabine, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, Idoxuridine, [SDV.BA.MVSA] Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, 0402 animal and dairy science, Valganciclovir, 04 agricultural and veterinary sciences, General Medicine, 040201 dairy & animal science, Virology, 3. Good health, horse, chemistry, circulation, France, Viral load, medicine.drug, Cidofovir
Abstract

International audience; Background: Equine coital exanthema (ECE) is an acute viral infection of horses caused by equid herpesvirus-3 (EHV-3). The presence of the virus and its economic impact is well described in different countries such as Argentina or Japan. However, even though it is included in the HBLB code of practice (UK) and in the list of diseases monitored by the RESPE (FR), only a few studies have been performed in Europe.Objectives: To determine the circulation of EHV-3 in France and measure the efficacy of new antiviral compounds against EHV-3.Study design: Retrospective field study and in vitro experiments.Methods: 71 field samples from suspected ECE cases, and collected between 2010 and 2021, were analysed by qPCR (DNA polymerase gene) and phylogenetic analysis (gG gene) was performed on 10 positive samples. Antiviral compounds (aciclovir, ganciclovir, valganciclovir, decitabine, idoxuridine, pritelivir, cidofovir, aphidicolin, vidarabine) previously described with antiviral properties against EHV-1, were evaluated using Real-Time Cell Analysis (RTCA) on equine dermal cells with the reference strain EHV-3 VR3522, cytopathic effect monitoring (microscopy) and viral load quantification (qPCR).Results: 16/71 (22%) suspected ECE cases were confirmed positive by PCR with 0 to 3 cases per year. French strains were clustered into two of the three observed phylogenic groups, but there was no correlation between the phylogeny and the time of collection or location. Aphidicolin was the most effective compound with an EC50 value of 2.43±0.02 µM (RTCA) and 1.63±0.48 µM (qPCR). Pritelivir and cidofovir were less potent molecules against EHV-3 (EC50 >50 µM).Main limitation: Antiviral compounds were tested against the reference strain only.Conclusions: This study demonstrates for the first time the presence of EHV-3 over a twelve-year period in France. In vitro studies show the antiviral efficacy of aphidicolin.

Published
2021
Full Text
View/download PDF

11. Identification and in vitro and in vivo characterization of a new equid herpesvirus‐1 DNA polymerase (ORF30) genotype associated with a C2254 / H752 strain in French horses

Author

Gabrielle Sutton, Edouard Guitton, Christel Marcillaud Pitel, Alexis Pléau, Alain Deslis, Stéphane Pronost, Christine Fortier, Erika Hue, Côme Thieulent, Romain Paillot, LABÉO, Pôle d’analyses et de recherche de Normandie (LABÉO), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), ImpedanCELL, Interactions Cellules Organismes Environnement (ICORE), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Réseau d'Epidémio-Surveillance en Pathologie Équine (RESPE), Plateforme d'Infectiologie Expérimentale (PFIE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), School of Equine and Veterinary Physiotherapy, and Writtle University College (WUC)

Subjects
[SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, biology, Strain (chemistry), 040301 veterinary sciences, DNA polymerase, 0402 animal and dairy science, 04 agricultural and veterinary sciences, General Medicine, 040201 dairy & animal science, Molecular biology, In vitro, 0403 veterinary science, In vivo, Genotype, biology.protein, Identification (biology), ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2021
Full Text
View/download PDF

12. Development of an assay using real time cell analysis for the measurement of equid herpesvirus 1 specific neutralizing antibody in horses after experimental infection or field vaccination

Author

Edouard Guitton, Gabrielle Sutton, Stéphane Pronost, Côme Thieulent, Alexis Pléau, Alain Deslis, Romain Paillot, Christine Fortier, Erika Hue, Barbara Buisson, Flora Carnet, Camille Normand, LABÉO, Pôle d’analyses et de recherche de Normandie (LABÉO), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), ImpedanCELL, Interactions Cellules Organismes Environnement (ICORE), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Plateforme d'Infectiologie Expérimentale (PFIE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), SEL EQUIN.VET, School of Equine and Veterinary Physiotherapy, Writtle University College (WUC), and Fonds Eperon OVERLORD N12-2017, Normandy County Council (17E01598/17EP04324), the IFCE (Institut Français du Cheval et de l’Equitation) grant number 2017-008, CENTAURE European project co-funded by Normandy County Council, European Union in the framework of the ERDF-ESF operational programme 2014-2020.

Subjects
[SDV.BIO]Life Sciences [q-bio]/Biotechnology, Serial dilution, biology, 040301 veterinary sciences, business.industry, [SDV.BA]Life Sciences [q-bio]/Animal biology, 0402 animal and dairy science, Horse, 04 agricultural and veterinary sciences, General Medicine, 040201 dairy & animal science, Virology, Neutralization, 3. Good health, 0403 veterinary science, Titer, Immune system, biology.protein, Medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Antibody, Seroconversion, business, Neutralizing antibody
Abstract

Background: Equid herpesvirus-1 (EHV-1) is one of the most important horse pathogens, which induces respiratory disease, myeloencephalopathy, abortion or still-birth. The measurement of EHV-1 neutralising (EHV-1-VN) antibodies using a neutralisation assay (NA) gives an indication of the immune response of horses in the field. Objectives: To develop a real time neutralisation assay (RTNA) using the xCELLigence® technology for the measurement of EHV-1-VN antibodies in serums from EHV-1 experimentally infected or vaccinated horses. Study design: Assay development and field trial. Methods: The RTNA based on E. Derm cells was developed using serums (n=48) taken daily (from Days 0 to 18 post-infection) from ponies experimentally infected with a field EHV-1 strain. This method was further evaluated using field serums (n=63) taken during an EHV-1/-4 vaccination campaign. RTNA results were compared to those obtained with the conventional EHV-1 NA on RK13 cells. Two-fold serial dilutions of serums were incubated with a defined concentration of the KyD EHV-1 strain before infection of E. Derm cells. The normalised cell index was monitored pre- and post-infection using the xCELLigence® technology. Conventional NA was performed using the same experimental methodology on RK13 cells and cytopathic effects were measured 72 hours post-infection. Results: Serum titres which induced 50% of EHV-1 neutralisation (NT50) were determined using a dose-response approach. The increase of the EHV-1 NT50 was similar to the increase in titre measured with the conventional NA (R²=0.79). Seroconversion was detected between Days 0 and 18 post-infection for all infected ponies with both methods. The NT50 values measured for EHV-1/-4 vaccinated horse serums were also positively correlated with conventional NA titres (R²=0.83). Main limitations: EHV-1/-4 cross-reactivity will require further investigation. Each assay used different cells. Conclusion: While the conventional NA is time consuming, requires subjective measurements and provides semi-quantitative discrete ranked titres (e.g. 4, 8 etc.), the EHV-1-VN RTNA is an automated, sensitive and objective measurement that reports continuous titres.

Published
2021
Full Text
View/download PDF

13. Equine Herpesvirus 1 Variant and New Marker for Epidemiologic Surveillance, Europe, 2021

Author

Anne Couroucé, Ann Cullinane, Marie Garvey, Gabrielle Sutton, Christel Marcillaud-Pitel, Pierre-Hugues Pitel, Romain Paillot, Camille Normand, Sophie Castagnet, Christine Fortier, Erika Hue, Loïc Legrand, Flora Carnet, Stéphane Pronost, LABÉO, Pôle d’analyses et de recherche de Normandie (LABÉO), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Irish Equine Centre (IEC), Réseau d'Epidémio-Surveillance en Pathologie Équine (RESPE), and Writtle University College (WUC)

Subjects
Microbiology (medical), Epidemiology, viruses, 030231 tropical medicine, Equine herpesvirus 1, Infectious and parasitic diseases, RC109-216, equine herpesvirus 1, 03 medical and health sciences, Open Reading Frames, 0302 clinical medicine, Polymorphism (computer science), Virus strain, Research Letter, Animals, Horses, Neurologic disease, 030304 developmental biology, 0303 health sciences, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, biology, Outbreak, Epidemiologic Surveillance, Herpesviridae Infections, Equine Herpesvirus 1 Variant and New Marker for Epidemiologic Surveillance, Europe, 2021, biology.organism_classification, Virology, 3. Good health, Europe, Open reading frame, Infectious Diseases, Spain, Mutation (genetic algorithm), [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Epidemiological Monitoring, Medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Horse Diseases, Valencia, Herpesvirus 1, Equid
Abstract

International audience; Equine herpesvirus 1 isolates from a 2021 outbreak of neurologic disease in Europe have a mutation, A713G, in open reading frame 11 not detected in 249 other sequences from equine herpesvirus 1 isolates. This single-nucleotide polymorphism could help identify horses infected with the virus strain linked to this outbreak.

Published
2021
Full Text
View/download PDF

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

Author

Christine Fortier, Erika Hue, Aymeric Hans, Pierre-Olivier Vidalain, Patrick Dallemagne, Romain Paillot, Peggy Suzanne, Stéphane Pronost, Côme Thieulent, Hélène Munier-Lehmann, Stéphan Zientara, LABÉO, Pôle d’analyses et de recherche de Normandie (LABÉO), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), ImpedanCELL, Interactions Cellules Organismes Environnement (ICORE), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-CHU Caen, Normandie Université (NU), Chimie et Biocatalyse, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Virologie UMR1161 (VIRO), École nationale vétérinaire d'Alfort (ENVA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de pathologie équine de Dozulé, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Biologie cellulaire des infections virales – Cell biology of viral infection, Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), École nationale vétérinaire - Alfort (ENVA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de santé animale, sites de Maisons-Alfort et de Normandie, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), HUE, Erika, École nationale vétérinaire - Alfort (ENVA)-Laboratoire de santé animale, sites de Maisons-Alfort et de Normandie, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Equid herpesvirus-1, Chemical library screening, Decitabine, lcsh:Computer applications to medicine. Medical informatics, Virus, Chemical library, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, Molecule, Research article, Antiviral, lcsh:Science (General), Data Article, 030304 developmental biology, Real-time cell assay, 0303 health sciences, Multidisciplinary, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, Focused Impedance Measurement, Chemistry, screening, [SDV.BA.MVSA] Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, Valganciclovir, Virology, In vitro, 3. Good health, lcsh:R858-859.7, 030217 neurology & neurosurgery, lcsh:Q1-390, medicine.drug
Abstract

International audience; Data presented in this article are associated with the research article “Identification of antiviral compounds against equid herpesvirus-1 using real-time cell assay screening: efficacy of decitabine and valganciclovir alone and in combination” [1]. These data correspond to the in vitro screening of 2,891 potential antiviral compounds against equid herpesvirus-1 (EHV-1) based on impedance measurements using the xCELLigence® RTCA MP System. This dataset includes compounds from three different libraries: i) 1,199 compounds from the Prestwick® Chemical Library, which contains mostly US Food and Drug Administration approved drugs (Prestwick® Chemical, Illkirch, France); ii) 1,651 compounds from the Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN, Caen, France); iii) 41 compounds (called herein in-house antiviral library) selected for their effects against different human viruses. Compounds effective against EHV-1 were selected using the area under normalised curves (AUCn) and the time required for the Cell Index to decrease by 50% after virus infection (CIT50). The full dataset from the screen is made publicly available for further analyses.

Published
2020
Full Text
View/download PDF

15. Identification of a New Equid Herpesvirus 1 DNA Polymerase (ORF30) Genotype with the Isolation of a C2254/H752 Strain in French Horses Showing no Major Impact on the Strain Behaviour

Author

Edouard Guitton, Christine Fortier, Erika Hue, Christel Marcillaud-Pitel, Alexis Pléau, Romain Paillot, Côme Thieulent, Gabrielle Sutton, Stéphane Pronost, Alain Deslis, LABÉO, Pôle d’analyses et de recherche de Normandie (LABÉO), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), ImpedanCELL, Interactions Cellules Organismes Environnement (ICORE), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Réseau d'Epidémio-Surveillance en Pathologie Équine (RESPE), Plateforme d'Infectiologie Expérimentale (PFIE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), School of Equine and Veterinary Physiotherapy, Writtle University College (WUC), Fonds Eperon OVERLORD N12-2017, Normandy County Council (17E01598/17EP04324), the IFCE (Institut Francais du Cheval et de l'Equitation) grant number 2017-008, CENTAURE European project co-funded by Normandy County Council, and European Union in the framework of the ERDF-ESF operational programme 2014-2020.

Subjects
0301 basic medicine, Male, viruses, lcsh:QR1-502, DNA-Directed DNA Polymerase, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, lcsh:Microbiology, Disease Outbreaks, 0403 veterinary science, chemistry.chemical_compound, EHV-1, antivirals, Genotype, education.field_of_study, Strain (chemistry), 04 agricultural and veterinary sciences, Herpesviridae Infections, Viral Load, 3. Good health, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, France, Viral load, medicine.drug, Herpesvirus 1, Equid, Ganciclovir, Aphidicolin, 040301 veterinary sciences, Population, Biology, DNA polymerase, Article, 03 medical and health sciences, Open Reading Frames, Viral Proteins, Virology, medicine, Animals, Typing, Horses, ORF30, Viral shedding, education, Retrospective Studies, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, 030104 developmental biology, chemistry, experimental infection, Mutation, Horse Diseases, equid herpesvirus 1
Abstract

Equid herpesvirus 1 is one of the most common viral pathogens in the horse population and is associated with respiratory disease, abortion and still-birth, neonatal death and neurological disease. A single point mutation in the DNA polymerase gene (ORF30: A2254G, N752D) has been widely associated with neuropathogenicity of strains, although this association has not been exclusive. This study describes the fortuitous isolation of a strain carrying a new genotype C2254 (H752) from an outbreak in France that lasted several weeks in 2018 and involved 82 horses, two of which showed neurological signs of disease. The strain was characterised as UL clade 10 using the equid herpesvirus 1 (EHV-1) multi-locus sequence typing (MLST) classification but has not been identified or isolated since 2018. The retrospective screening of EHV-1 strains collected between 2016 and 2018 did not reveal the presence of the C2254 mutation. When cultured in vitro, the C2254 EHV-1 strain induced a typical EHV-1 syncytium and cytopathic effect but no significant difference was observed when compared with A2254 and G2254 EHV-1 strains. An experimental infection was carried out on four Welsh mountain ponies to confirm the infectious nature of the C2254 strain. A rapid onset of marked respiratory disease lasting at least 2 weeks, with significant virus shedding and cell-associated viraemia, was observed. Finally, an in vitro antiviral assay using impedance measurement and viral load quantification was performed with three antiviral molecules (ganciclovir (GCV), aciclovir (ACV) and aphidicolin (APD)) on the newly isolated C2254 strain and two other A/G2254 field strains. The three strains showed similar sensitivity to ganciclovir and aphidicolin but both C2254 and A2254 strains were more sensitive to aciclovir than the G2254 strain, based on viral load measurement.

Published
2020
Full Text
View/download PDF

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

Author

Pierre-Olivier Vidalain, Patrick Dallemagne, Aymeric Hans, Côme Thieulent, Christine Fortier, Erika Hue, Stéphan Zientara, Stéphane Pronost, Romain Paillot, Hélène Munier-Lehmann, Gabrielle Sutton, LABÉO, Pôle d’analyses et de recherche de Normandie (LABÉO), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), ImpedanCELL, Interactions Cellules Organismes Environnement (ICORE), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-CHU Caen, Normandie Université (NU), Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Virologie UMR1161 (VIRO), École nationale vétérinaire d'Alfort (ENVA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Chimie et Biocatalyse, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Laboratoire de pathologie équine de Dozulé, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), ANSES, Laboratoire de Santé Animale - site de Dozulé, Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), This work was supported by LABÉO, IFCE (Institut Français du Cheval et de l'Equitation, project AMIE), Fonds Eperon (project N87–2014, N07–2015, N07–2016, N13–2017 and N62-2017), Région Normandie (CPER R25 P3) and CENTAURE European project co-funded by Normandy County Council, European Union in the framework of the ERDF-ESF operationnal programme 2014–2020., Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), École nationale vétérinaire - Alfort (ENVA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et épidémiologie des maladies équines (PhEED), Laboratoire de santé animale, sites de Maisons-Alfort et de Normandie, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), HUE, Erika, École nationale vétérinaire - Alfort (ENVA)-Laboratoire de santé animale, sites de Maisons-Alfort et de Normandie, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Aphidicolin, Ganciclovir, Equid herpesvirus-1, 030106 microbiology, Chemical library screening, Decitabine, Antiviral Agents, Cell Line, 03 medical and health sciences, chemistry.chemical_compound, Virology, Drug Discovery, Medicine, Animals, Valganciclovir, Synergism, Horses, Antiviral, Pharmacology, Real-time cell assay, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, business.industry, Idoxuridine, [SDV.BA.MVSA] Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, Drug Synergism, Deoxycytidine kinase, Herpesviridae Infections, 3. Good health, High-Throughput Screening Assays, Drug Combinations, 030104 developmental biology, chemistry, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Deoxycytidine, Rabbits, business, Nucleoside, medicine.drug, Herpesvirus 1, Equid
Abstract

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

Published
2020
Full Text
View/download PDF

17. Porcine Reproductive and Respiratory Syndrome Virus Interferes with Swine Influenza A Virus Infection of Epithelial Cells

Author

Stéphane Pronost, Patricia Renson, François Meurens, Joëlle Dupont, Nicolas Bertho, Gaëlle Simon, Romain Paillot, Olivier Bourry, Caroline Hervet, Laurence Dubreil, Erika Hue, Georges Saade, Jianzhong Zhu, Déborah Ménard, Biologie, Epidémiologie et analyse de risque en Santé Animale (BIOEPAR), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de Ploufragan-Plouzané-Niort [ANSES], Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), LABÉO, Pôle d’analyses et de recherche de Normandie (LABÉO), ImpedanCELL, Interactions Cellules Organismes Environnement (ICORE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), College of Veterinary Medicine, Comparative Medicine Research Institute, Yangzhou University-Yangzhou University, Physiopathologie Animale et bioThérapie du muscle et du système nerveux (PAnTher), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
0301 basic medicine, pig, MESH: Porcine Reproductive and Respiratory Syndrome, animal diseases, viruses, 030106 microbiology, Immunology, Porcine Reproductive and Respiratory Syndrome, interference, lcsh:Medicine, swIAV, medicine.disease_cause, Virus, Article, 03 medical and health sciences, Interferon, Drug Discovery, medicine, Influenza A virus, Pharmacology (medical), Respiratory system, Receptor, Pharmacology, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, biology, epithelial cell, lcsh:R, Porcine reproductive and respiratory syndrome virus, biology.organism_classification, medicine.disease, Virology, Epithelium, coinfection, 3. Good health, 030104 developmental biology, Infectious Diseases, medicine.anatomical_structure, PRRSV, Coinfection, Swine Influenza A viruses, medicine.drug
Abstract

International audience; Respiratory infections are still a major concern in pigs. Amongst the involved viruses, the porcine reproductive and respiratory syndrome virus (PRRSV) and the swine influenza type A virus (swIAV) have a major impact. These viruses frequently encounter and dual infections are reported. We analyzed here the molecular interactions between viruses and porcine tracheal epithelial cells as well as lung tissue. PRRSV-1 species do not infect porcine respiratory epithelial cells. However, PRRSV-1, when inoculated simultaneously or shortly before swIAV, was able to inhibit swIAV H1N2 infection, modulate the interferon response and alter signaling protein phosphorylations (ERK, AKT, AMPK, and JAK2), in our conditions. SwIAV inhibition was also observed, although at a lower level, by inactivated PRRSV-1, whereas acid wash treatment inactivating non-penetrated viruses suppressed the interference effect. PRRSV-1 and swIAV may interact at several stages, before their attachment to the cells, when they attach to their receptors, and later on. In conclusion, we showed for the first time that PRRSV can alter the relation between swIAV and its main target cells, opening the doors to further studies on the interplay between viruses. Consequences of these peculiar interactions on viral infections and vaccinations using modified live vaccines require further investigations.

Published
2020
Full Text
View/download PDF

18. Further Evidence for in Utero Transmission of Equine Hepacivirus to Foals

Author

J. Tapprest, Marc Foursin, Romain Paillot, Christel Marcillaud-Pitel, Pierre-Hugues Pitel, Christine Fortier, Erika Hue, Bertrand Saunier, Stéphane Pronost, LABÉO, Pôle d’analyses et de recherche de Normandie (LABÉO), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Réseau d'Epidémio-Surveillance en Pathologie Équine (RESPE), Physiopathologie et épidémiologie des maladies équines (PhEED), Laboratoire de santé animale, sites de Maisons-Alfort et de Normandie, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Clinique Équine de la Boisrie, Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), ANSES, Laboratoire de Santé Animale - site de Dozulé, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Cirrhosis, Genes, Viral, Hepacivirus, Hepatitis C virus, 030106 microbiology, Population, medicine.disease_cause, 03 medical and health sciences, in utero transmission, Virology, Prevalence, Medicine, Animals, MESH: Hepacivirus, Horses, education, Phylogeny, education.field_of_study, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, biology, equine hepacivirus, Base Sequence, business.industry, Transmission (medicine), Communication, Horse, biology.organism_classification, medicine.disease, Hepatitis C, Infectious Disease Transmission, Vertical, 3. Good health, horse, Flavivirus, 030104 developmental biology, Infectious Diseases, In utero, non-primate hepacivirus, fetuses, Horse Diseases, MESH: Horse Diseases, business
Abstract

International audience; (1) Background: Equine hepacivirus (EqHV), also referred to as non-primate hepacivirus (NPHV), infects horses—and dogs in some instances—and is closely related to hepatitis C virus (HCV) that has infected up to 3% of the world’s human population, causing an epidemic of liver cirrhosis and cancer. EqHV also chronically infects the liver of horses, but does not appear to cause serious liver damages. Previous studies have been looking to identify route(s) of EqHV transmission to and between horses. (2) Methods: In this retrospective study, we sought to evaluate the prevalence of vertical transmission taking place in utero with measuring by quantitative RT-PCR the amounts of EqHV genome in samples from 394 dead foals or fetuses, paired with the allantochorion whenever available. (3) Results: Detection of EqHV in three foals most likely resulted from a vertical transmission from the mares to the fetuses, consistent with the in utero transmission hypothesis. In support of this observation, the presence of EqHV genome was found for the first time in two of the allantochorions. (4) Conclusions: As seemingly benign viruses could turn deadly (e.g., Zika flavivirus) and EqHV happens to have infected a significant proportion of the world’s horse herds, EqHV infectious cycle should be further clarified.

Published
2019
Full Text
View/download PDF

19. Hepacivirus and the 'new triade' : Further evidence for in utero transmission of equine hepacivirus to foals

Author

Stéphane Pronost, Christine Fortier, Christel Marcillaud Pitel, Jackie Tapprest, Marc Foursin, Bertrand Saunier, Pierre-Hugues Pitel, Romain Paillot, Erika HUE, LABÉO, Pôle d’analyses et de recherche de Normandie (LABÉO), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Réseau d'Epidémio-Surveillance en Pathologie Équine (RESPE), Laboratory for Animal Health in Normandy, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Clinique Équine de la Boisrie, Virologie Structurale - Structural Virology, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health
Abstract

International audience; Equine hepacivirus (EqHV), also referred to as non-primate hepacivirus (NPHV), infects horses —and dogs in some instances— and is closely related to hepatitis C virus (HCV) that has infected up to 3 % of the world’s human population, causing an epidemic of liver cirrhosis and cancer. EqHV is also chronically infecting the liver of horses, but does not appear to cause serious liver damages. Recent work often associates two other viruses, Theiler Disease Associated Virus (TDAV) and Pegivirus (EqPV) to this research during hepatic syndrome. If the name of the hepatic triad has emerged in recent years, the recent discovery of a new virus, a potentially involved equine parvovirus, raises new questions. Among these, the mode of transmission of these viruses is an essential issue. Previous studies have been looking to identify route(s) of EqHV transmission to and between horses. In a retrospective study, we sought to evaluate the prevalence of vertical transmission taking place in utero with measuring by quantitative RT-PCR the amounts of EqHV genome in samples from 394 dead foals or fetuses, paired with the allantochorion whenever available. Detection of EqHV in three foals most likely resulted from a vertical transmission from the mares to the fetuses, consistent with the in-utero transmission hypothesis. In support of this observation, the presence of EqHV genome was found for the first time in two of the allantochorions. If the first transmission tracks emerge for EqHV, studies are needed for the "triad" or even the "tetrad".

Published
2019

20. Impedance & other original tools for cellular models

Author

Stéphane Pronost, Côme Thieulent, Erika HUE, Gabrielle Sutton, Flora Carnet, Christine Fortier, Emilie Brotin, Laurent Poulain, Romain Paillot, Christophe Denoyelle, LABÉO, Pôle d’analyses et de recherche de Normandie (LABÉO), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), ImpedanCELL, Interactions Cellules Organismes Environnement (ICORE), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Normandie Université (NU)-CHU Caen, Normandie Université (NU), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), and HUE, Erika

Subjects
[SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, [SDV.BA.MVSA] Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health
Abstract

International audience; In the fields of biology and human and veterinary medicine, much progress has been made over the past 20 years. The new areas of investigation are often linked to technological progress and if big data has not revealed all its secrets, or if 3D bioprinters have not proposed new study models in all expected domains, many innovative technologies have enter in the laboratories of the 21st century. Thus, the cellular culture often presented as a long and tedious technique knows a small revolution with the arrival of real-time technologies. After the Real Time PCR techniques in molecular biology, Real Time Cell Analysis (RTCA) in cell biology opens up new perspectives in many applications. An original platform name Impedancell, labeled in 2019 by the French IBISA (French certification body for technologies applied to research in the living world) was built in Normandy to manage this new paradigm.ImpedanCELL is an innovative and original core facility for studying real-time high-throughput cellular activity using impedance measurement (xCELLigence technology) and real-time cellular imaging. It is localised on two different geographical sites in Caen (Normandy, France): Comprehensive Cancer Center F. Baclesse for all non-microbiology applications and LABÉO (Equine Normandy Equine Valley Biotechnology platform and BIOTARGEN research team) for all applications in virology and in bacteriology (biosafety level 2). The core facility is equipped with cutting-edge technologies (3 xCELLigence MP, 1 xCELLigence DP, 1 iCELLigence, 1 Cellavista, 2 Incucytes…) allowing the study of adhesion, proliferation, cell death, migration and invasion in various domains including oncology, neurosciences, toxicology, immunology, marine biology, virology and bacteriology. In line with one ImpedanCELL’s mission, the core facility is open to any scientists with high-throughput study needs for dynamic tracking of real-time cellular behaviour. ImpedanCELL is open to collaborations and services for both academic and industrial partners and offers theoretical and practical courses. Two different applications performed on each site are presented with the advantage of this new technology for two areas of expertise in each laboratory: equine virology on the one hand and human cancer research on the other.Among the infectious agents found in the equine species, herpesviruses are certainly among those causing the greatest economic losses in the world. Equid alpha-herpesviruses (EHV) are responsible for different diseases in equine population. EHV-1 causes respiratory diseases, abortions and nervous disorders, EHV-4 causes respiratory diseases and sporadic abortion while EHV-3 is responsible of equine coital exanthema. In view of the lack of efficacy of vaccines against EHV-1 and EHV-4 and in the absence of vaccines against EHV-3, the use of antiviral treatment is of great interest. Our team recently documented the interest of the Real-Time Cell Analysis technology to monitor the cytopathic effects (CPE) induced by these viruses on equine dermal cells, and established the efficacy of this method to evaluate the antiviral effect of aciclovir (ACV) and ganciclovir (GCV). In addition, RTCA technology has also been found suitable for high throughput screening of small molecules against EHV , allowing identification of several molecules of interest as a new antiviral against EHV, among them spironolactone is a potential candidate.1In the field of oncology, repositioning is also an interesting approach and, in this respect, the RTCA are technologies of interest. The development of direct Mcl-1 inhibiting molecules constitutes a major challenge for the success of Bcl-xL targeting strategies in ovarian carcinoma. After computational modelling to identify molecules able to target the Mcl 1 hydrophobic pocket, a high throughput functional screening assay based on xCELLigence technology was implemented to evaluate the ability of designed and synthesized molecules called oligopyridines to sensitize ovarian carcinoma cells (in addiction to both Bcl-xL and Mcl-1) to Bcl xL-targeting strategies. After establishing structure-activity relationships and identifying a potent lead (hit) called Pyridoclax, surface plasmon resonance assay demonstrated that pyridoclax directly binds to Mcl-1. Without cytotoxic activity when administered as a single agent, pyridoclax induced apoptosis in combination with Bcl-xL targeting siRNA or with ABT 737 in ovarian cancer cells. These results open up interesting perspectives for the clinical use of Mcl-1 inhibitors to improve the clinical management of ovarian cancer.2 Overall, these two high-throughput studies demonstrated the interest to use impedance based technologies to identify some pertinent targets and molecules for therapeutic intervention in the context of the precision medicine in ovarian cancer an in EHV infectious disease in horses. Our study confirms the efficiency of RTCA to monitor CPE formation induced by EHV-1 on E. Derm cells, and further extends this tool to EHV-4 and EHV-3. In the infectious field, applications in bacteriology and in particular studies on biofilms also use this technology which facilitates the screening of antibiotics. The use in the field of immunology is also booming. While the interest of screening by impedance measurements is well established, real-time monitoring of cell development under the microscope remains essential. Engineers have understood this, which explains the arrival in 2020 of one technology coupling these two approaches.

Published
2019

21. Real-Time monitoring of Equid alphaherpesviruses infectivity in equine dermal cell based on impedance measurements: effects of aciclovir and ganciclovir treatments

Author

Côme Thieulent, Erika Hue, Christine Fortier, Peggy Suzanne, Stephan Zientara, aymeric, Hélène Munier-Lehmann, Guillaume Fortier, Pierre-Hugues Pitel, Pierre-Olivier Vidalain, Stéphane Pronost, LABÉO, Pôle d’analyses et de recherche de Normandie (LABÉO), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), ImpedanCELL, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Virologie UMR1161 (VIRO), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Laboratoire de pathologie équine de Dozulé, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Chimie et Biocatalyse, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Interactions Cellules Organismes Environnement (ICORE), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Laboratoire de santé animale, sites de Maisons-Alfort et de Normandie, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-CHU Caen, Normandie Université (NU), Institut National de la Recherche Agronomique (INRA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-École nationale vétérinaire d'Alfort (ENVA), and Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]

Subjects
[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2018

22. Real-Time monitoring of Equid alphaherpesviruses infectivity in equine dermal cell based on impedance measurements: effects of aciclovir and ganciclovir treatments (IBCA)

Author

Côme Thieulent, Erika Hue, Christine Fortier, Peggy Suzanne, Stephan Zientara, Hélène Munier-Lehmann, aymeric, Pierre-Hugues Pitel, Pierre-Olivier Vidalain, Stéphane Pronost, LABÉO, Pôle d’analyses et de recherche de Normandie (LABÉO), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), ImpedanCELL, Interactions Cellules Organismes Environnement (ICORE), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-CHU Caen, Normandie Université (NU), Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Virologie UMR1161 (VIRO), Institut National de la Recherche Agronomique (INRA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-École nationale vétérinaire d'Alfort (ENVA), Chimie et Biocatalyse, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Laboratoire de pathologie équine de Dozulé, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Génomique Virale et Vaccination, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de santé animale, sites de Maisons-Alfort et de Normandie, and Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)

Subjects
viruses, [SDV]Life Sciences [q-bio], [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology
Abstract

International audience; Five herpesvirus have been reported to infect horses and 3 belong to the Alphaherpesvirinae subfamily (equine herpesvirus-1, EHV-4 and EHV-3). Among them, EHV-1 is the most pathogenic and causes respiratory disease in young horses, abortion in mares, neonatal death and neurologic damages, also call equine herpesvirus myeloencephalopathy. EHV-4, also named the rhinopneumonia virus, is closely related to EHV-1 but mostly causes respiratory disease and only sporadic abortion and neonatal infection in horses. EHV-3 is distinct from previous viruses and is responsible for equine coital exanthema, characterized by formation of papules, pustules, ulcers and vesicles on the external genitalia of horses. The equine industry economical loss linked to EHV infection is significant, which warrants surveillance and prophylaxis. Currently, no antiviral molecule has a marketing authorization for equine species despite critically needs, warranting the development or adaptation of drugs that are effective against equine viruses.The aims of this work were 1) to investigate the efficacy of Real-Time Cell Analysis (RTCA) system to monitor EHV infections in equine dermal cells 2) to assess the effectiveness of acyclovir (ACV) and ganciclovir (GCV) against EHV-1, EHV-4 and EHV-3 by RTCA system and 3) to investigate the capacity of RTCA system for the screening of compounds library in order to identified new inhibitors of these viruses. To confirm results achieved, monitoring of cell morphology by microscopy and quantification of viral loads were perform in parallel.Antiviral effect of ACV or GCV against the EHV-1 KyD strain was evaluated by RTCA. Results showed that ACV and GCV prevented the impedance decrease induced by EHV-1 infection in a dose-dependent manner and EC50 measured were 9.88 ± 2.14 µg/ml and 0.62 ± 0.49 µg/ml, respectively. The ACV and GCV EC50 against EHV-4 were 17.38 ± 5.95 µg/ml and 2.79 ± 0.25 µg/ml, respectively. Against EHV-3, the ACV and GCV EC50 were 15.23 ± 2.85 µg/ml and 1.86 ± 0.46 µg/ml, respectively. All the data were confirm by qPCR and microscopy observation. The screening of compounds library allowed identifying several molecules with an antiviral activity needing further investigation.This study confirms the efficiency of RTCA to monitor cytopathic effect formation induced by equine alphaherpesviruses on E. Derm cells in real-time. In this model, GCV was shown to be the most effective against all viruses used to infect E. Derm cells. This technology aims to complement and support conventional methods used in the field of virology.

Published
2018

23. Epidemiology and molecular detection of equine herpesviruses in western Algeria in 2011

Author

Stéphane Pronost, Aymeric Hans, E. Morilland, Loïc Legrand, Christine Fortier, Erika Hue, F. Laabassi, University of Batna Hadj Lakhder [Algeria], LABÉO, Pôle d’analyses et de recherche de Normandie (LABÉO), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Unité de virologie et parasitologie équine, Laboratoire de pathologie équine de Dozulé, and Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)

Subjects
0301 basic medicine, 040301 veterinary sciences, Biology, Alphaherpesvirinae, Horse, Microbiology, 0403 veterinary science, 03 medical and health sciences, Gammaherpesvirinae, medicine, Animals, Arteritis, Horses, Nose, Respiratory viruses, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, General Veterinary, Incidence (epidemiology), Respiratory infection, 04 agricultural and veterinary sciences, General Medicine, medicine.disease, Virology, 3. Good health, qPCR, Equine herpesvirus, 030104 developmental biology, medicine.anatomical_structure, Algeria, Respiratory virus, Horse Diseases, Viral load
Abstract

International audience; An episode of acute equine respiratory infection was reported in western Algeria (Tiaret province) between February and March 2011, affecting a large population of horses. Nasal swabs (n=100) were taken from horses aged between 1 and 27 years, presenting with cough and mucopurulent nasal discharge. The prevalence of equine respiratory virus infections was examined using quantitative polymerase chain reaction (qPCR). One, or more, of four equine respiratory viruses were detected in the nasal swabs of 90 of 100 horses (90%) and the detection rate of equine herpesvirus type 1 (EHV-1), equine herpesvirus type 4 (EHV-4), equine herpesvirus type 2 (EHV-2) and equine herpesvirus type 5 (EHV-5) were 2%, 14%, 90% and 75%, respectively. Equine influenza virus and equine arteritis virus were not detected in any samples. Among the 90 infected horses, 70 were coinfected with EHV-2 and EHV-5 and 14 others were co-infected with EHV-4, EHV-2 and EHV-5. The present study shows a positivity rate of 97.3% for EHV-5 in young horses aged

Published
2017
Full Text
View/download PDF

24. Hay dust particles measured by flow cytometry in steamed versus dry hay

Author

Marie Orard, Erika Hue, Maryline Guillamin, Meriel Moore-Colyer, Anne Couroucé, Laurent Couëtil, Magali Demoor, LABÉO, Pôle d’analyses et de recherche de Normandie (LABÉO), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Biologie des Organismes et Ecosystèmes Aquatiques (BOREA), Normandie Université (NU)-Normandie Université (NU)-Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Royal Agricultural University (RAU), Nutrition PhysioPathologie et Pharmacologie (NP3), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), College of Veterinary Medicine, and Purdue University [West Lafayette]

Subjects
[SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2017

25. Real-time monitoring of Equid herpesviruses infectivity in equine dermal cell based on impedance measurements

Author

Stéphan Zientara, Aymeric Hans, Christine Fortier, Erika Hue, Hélène Munier-Lehmann, Peggy Suzanne, Stéphane Pronost, Pierre-Hugues Pitel, Guillaume Fortier, Pierre-Olivier Vidalain, LABÉO, Pôle d’analyses et de recherche de Normandie (LABÉO), Unité de Recherche Risques Microbiens (U2RM), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Fondation Hippolia, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Virologie UMR1161 (VIRO), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Laboratoire de pathologie équine de Dozulé, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Chimie et Biocatalyse, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire d'Alfort (ENVA), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)

Subjects
Infectivity, Programmed cell death, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, 040301 veterinary sciences, Cell growth, Chemistry, Equine, viruses, 0402 animal and dairy science, 04 agricultural and veterinary sciences, 040201 dairy & animal science, Virology, Virus, 3. Good health, 0403 veterinary science, Cell culture, Cell adhesion, Viral load, Cytopathic effect
Abstract

International audience; In virology, different conventional methods are commonly used for virus titration and infectivity studies. Most of them are based on direct examination of viral cytopathic effect, which is time consuming, tedious and requires an endpoint reading. The RTCA xCELLigence system (ACEA Biosciences) has been developed to follow cellular events and their dynamics in real time using a micro-electrical biosensor technology. The aim of this study was to evaluate the feasibility of using this biosensor technology to measure the effect of different equid herpesviruses on equine dermal cell cultures, with or without antiviral acyclovir treatment. Cells were infected with EHV-1 (VR700), EHV-4 (VR2230), EHV-2 (VR701) or EHV-3 (VR352). The viral effects were monitored by 3 different methods: impedance measurements (RTCA), cytopathic effects recording (microscopy) and viral load quantification (qPCR). The RTCA technology showed a dose dependent drop of the cellular index induced by specific impedance variations measured during growth of each virus tested. These results correlated with the cytopathic effect induced by the different herpesvirus species, as well as viral loads measured by qPCR. For example, after 3 days of incubation with EHV-1, RTCA results showed an increase of the cellular index from 0% (infection without antiviral) to 45% and 100% in presence of Acyclovir (10μl/mL and 100 μg/mL, respectively). These results are correlated with the decreased of viral load measured in the presence of Acyclovir: 1010 genome copies/mL with EHV-1 only, 106 copies/mL with EHV-1 + Acyclovir 10 μg/ mL and 105 copies/mL with EHV-1 + Acyclovir 100 μg/ mL. In conclusion, the cellular impedance monitoring system is a new real-time method to monitor cell growth and viral proliferation in cell cultures. This technology is well adapted for high-throughput screening of antiviral molecules. In fact, the xCELLigence system enables continuous impedance measurement and quantification of cell adhesion, proliferation, cell death and detachment during viral infection.

Published
2016
Full Text
View/download PDF

26. Development and Validation of a Quantitative PCR Method for Equid Herpesvirus-2 Diagnostics in Respiratory Fluids

Author

Guillaume Fortier, Loïc Legrand, Stéphane Pronost, Christine Fortier, Erika Hue, Aurélie M. Laurent, Yann F. Quesnelle, LABÉO, Pôle d’analyses et de recherche de Normandie (LABÉO), Unité de Recherche Risques Microbiens (U2RM), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), and Fondation Hippolia

Subjects
0301 basic medicine, titration, linearity, Rhadinovirus, General Chemical Engineering, Immunology, specificity, Computational biology, Quantitative RT-PCR, Real-Time Polymerase Chain Reaction, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Animals, Equine herpesvirus 2, Horses, Pcr analysis, validation, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, General Immunology and Microbiology, biology, General Neuroscience, Reproducibility of Results, equid herpesvirus-2, Herpesviridae Infections, Viral Load, biology.organism_classification, sensitivity, Virology, Biological materials, 3. Good health, Virus detection, horse, Tumor Virus Infections, 030104 developmental biology, Real-time polymerase chain reaction, PCR norm, limits of detection, Data presentation, Horse Diseases, Bronchoalveolar Lavage Fluid, limits of quantification, Plasmids
Abstract

International audience; The protocol describes a quantitative RT-PCR method for the detection and quantification of EHV-2 in equine respiratory fluids according to the NF U47-600 norm. After the development and first validation step, two distinct characterization steps were performed according to the AFNOR norm: (a) characterization of the qRT-PCR assay alone and (b) characterization of the whole analytical method. The validation of the whole analytical method included the portrayal of all steps between the extraction of nucleic acids and the final PCR analysis. Validation of the whole method is very important for virus detection by qRT-PCR in order to get an accurate determination of the viral genome load. Since the extraction step is the primary source of loss of biological material, it may be considered the main source of error of quantification between one protocol and another. For this reason, the AFNOR norm NF-U-47-600 recommends including the range of plasmid dilution before the extraction step. In addition, the limits of quantification depend on the source from which the virus is extracted. Viral genome load results, which are expressed in international units (IU), are easier to use in order to compare results between different laboratories. This new method of characterization of qRT-PCR should facilitate the harmonization of data presentation and interpretation between laboratories.

Published
2016
Full Text
View/download PDF

27. Influence of bronchoalveolar lavage volume on cytological profiles and subsequent diagnosis of inflammatory airway disease in horses

Author

Erika Hue, A. Couroucé-Malblanc, Pierre-Hugues Pitel, Marianne Depecker, Marie Orard, Eric Richard, LABÉO, Pôle d’analyses et de recherche de Normandie (LABÉO), Interactions Cellules Organismes Environnement (ICORE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Laboratoire de Physiopathologie Animale et Pharmacologie Fonctionnelle, Ecole Nationale Vétérinaire Agroalimentaire et de l'Alimentation Nantes Atlantique (ONIRIS), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Unité de Recherche Risques Microbiens (U2RM), Normandie Université (NU)-Normandie Université (NU), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), and Normandie Université (NU)

Subjects
0301 basic medicine, Pathology, medicine.medical_specialty, 040301 veterinary sciences, medicine.medical_treatment, Sodium Chloride, Horse, Bronchoalveolar Lavage, 0403 veterinary science, 03 medical and health sciences, Cytology, Medicine, Animals, Inflammatory airway disease, Horses, Saline, Lung, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, General Veterinary, medicine.diagnostic_test, business.industry, Bronchoalveolar lavage fluid, Contralateral lung, 04 agricultural and veterinary sciences, respiratory system, Respiration Disorders, respiratory tract diseases, 030104 developmental biology, Airway disease, Bronchoalveolar lavage, medicine.anatomical_structure, Volume (thermodynamics), [SDV.IMM]Life Sciences [q-bio]/Immunology, Animal Science and Zoology, Horse Diseases, business
Abstract

International audience; The aim of the study was to determine whether instillation of either 250 mL or 500 mL of saline for bronchoalveolar lavage (BAL) would influence cytological confirmation of inflammatory airway disease (IAD). Thirty client-owned Standardbred racehorses were sampled via endoscopy with 250 mL of saline in one lung and 500 mL in the contralateral lung. The procedure was repeated 72 h later, reversing the volume per lung. The proportions of BAL fluid (BALF) recovered were significantly higher and neutrophil percentages significantly lower with the larger volume. A poor agreement was found between methodologies in terms of final diagnosis, when based on proportions of neutrophils (>10% from at least one lung). Within the recommended range (250–500 mL), the instilled volume significantly influenced cytological profiles. Establishing specific BALF reference values is warranted.

Published
2016
Full Text
View/download PDF

28. Equine PBMC cytokines profile and efficacy of a Parapoxvirus ovis based-immunomodulator after in vitro α- and γ-EHV infection

Author

Romain Paillot, Eric Richard, Rudiger Raue, Guillaume Fortier, Stéphane Pronost, Christine Fortier, Erika Hue, LABÉO, Pôle d’analyses et de recherche de Normandie (LABÉO), Unité de Recherche Risques Microbiens (U2RM), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Animal Health Trust (AHT), Veterinary Medicine Research and Development, Zoetis, and Fondation Hippolia

Subjects
education.field_of_study, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, biology, 040301 veterinary sciences, Equine, Population, 0402 animal and dairy science, Horse, 04 agricultural and veterinary sciences, biology.organism_classification, 040201 dairy & animal science, Virology, Peripheral blood mononuclear cell, In vitro, 3. Good health, 0403 veterinary science, Immune system, Gene expression, Immunology, Parapoxvirus, Respiratory system, education
Abstract

International audience; Horses are usually infected during the first months of life by several equine herpesviruses, such as EHV-1, EHV-4 or EHV-2. The persistence of these respiratory viruses through establishment of latency, often characterised by an absence of clinical signs, represents a real risk to the horse population. Reactivation of latent EHV could cause disease in both carriers and naive animals in contact. A better understanding of the immune response to EHV infection is necessary to improve our methods of prevention and decrease the risk of transmission. The objectives of this study were 1/ to characterise the cytokine gene expression profile of PBMC after in vitro EHV infection (EHV-1, EHV-4 and EHV-2) and 2/ To determine the efficacy of the inactivated Parapoxvirus ovis (iPPVO), a known immunomodulator in horses , against these same viruses. PBMC were isolated from 3 horses and infected in vitro with EHV-1, EHV-4 or EHV-2, in the presence or absence of iPPVO. In vitro culture of PBMC with EHV-1, EHV-4, EHV-2 and iPPVO induced a significant increase of IFN-α, IFN-β and IFN-γ gene expression. Moreover, EHV-2 induced a significant increase of IL-1β, IL-6 and TNF-α mRNA. The presence of iPPVO induced an earlier and stronger expression of IFN-α, IFN-β and IFN-γ during EHV infection. The presence of iPPVO reduced also the inflammatory response induced by EHV-2. In conclusion, this study suggests that the presence of iPPVO potentiates the development of the immune response during infection EHV in vitro.

Published
2016
Full Text
View/download PDF

29. Do BALF cytokine profiles vary depending on the sampled lung in horses with unilateral IAD-consistent cytology?

Author

Erika HUE, Marie Orard, Marianne Depecker, Anne Couroucé-Malblanc, Romain Paillot, Stéphane Pronost, Eric Richard, LABÉO, Pôle d’analyses et de recherche de Normandie (LABÉO), Unité de Recherche Risques Microbiens (U2RM), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Laboratoire de Physiopathologie Animale et Pharmacologie Fonctionnelle, Ecole Nationale Vétérinaire Agroalimentaire et de l'Alimentation Nantes Atlantique (ONIRIS), and Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)

Subjects
[SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2015

30. Long-lasting airway inflammation associated with equid herpesvirus-2 in experimentally challenged horses

Author

Christine Fortier, Erika Hue, Didier Pottier, Kerstin Borchers, Eric Richard, Pierre Lekeux, Laurent Lemaitre, Guillaume Fortier, Stéphane Pronost, Etienne Thiry, Laboratoire Frank Duncombe, Interactions Cellules Organismes Environnement (ICORE), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Unité de Recherche Risques Microbiens (U2RM), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Groupe Régional d'Etudes sur le CANcer (GRECAN), Normandie Université (NU)-Normandie Université (NU)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-IFR146, Mérial [Lyon], Mérial, Université de Liège, Fachbereich Veterinärmedizin, and Freie Universität Berlin

Subjects
Rhadinovirus, 040301 veterinary sciences, medicine.medical_treatment, Horse, 0403 veterinary science, 03 medical and health sciences, Equid herpesvirus 2, Adrenal Cortex Hormones, medicine, Animals, Equine herpesvirus 2, Inflammatory airway disease, Horses, Respiratory system, Respiratory Tract Infections, 030304 developmental biology, Inflammation, 0303 health sciences, Tracheal inflammation, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, General Veterinary, biology, Immunosuppression, Herpesviridae Infections, 04 agricultural and veterinary sciences, biology.organism_classification, Neutrophilia, 3. Good health, Tumor Virus Infections, Real-time polymerase chain reaction, Concomitant, Immunology, Horse Diseases, Animal Science and Zoology, medicine.symptom, Bronchoalveolar Lavage Fluid, Nested polymerase chain reaction, Immunosuppressive Agents
Abstract

International audience; The aim of this trial was to investigate the putative involvement of equid herpesvirus 2 (EHV-2) in airway inflammation of adult horses. Six horses received corticosteroid treatment, before either mock infection (n = 2) or EHV-2 strain LK4 inoculation (n = 4). These four horses were also submitted to immunosuppression 84 days post inoculation. EHV-2 was detected by quantitative PCR in respiratory samples up to respectively 21 days and 14 days. Nested PCR, cloning and sequencing allowed the detection of five different ‘field’ strains throughout the trial. Neutrophils proportions were transiently increased in respiratory fluids; neutrophilia being significantly associated with concomitant EHV-2 detection. The laboratory findings reproduced in this trial were compatible with sub-clinical lower airway inflammation and suggest that EHV-2 infection should be suspected when investigating poorly-performing horses.

Published
2013
Full Text
View/download PDF

31. Update on equine gammaherpesviruses

Author

Eric Richard, Stéphane Pronost, Erika HUE, Guillaume Fortier, HUE, Erika, and LABÉO, Pôle d’analyses et de recherche de Normandie (LABÉO)

Subjects
[SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, [SDV.BA.MVSA] Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2013

32. Equine gammaherpesviruses: pathogenesis, epidemiology and diagnosis

Author

Eric Richard, Stéphane Pronost, Erika HUE, Guillaume Fortier, HUE, Erika, and LABÉO, Pôle d’analyses et de recherche de Normandie (LABÉO)

Subjects
[SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, [SDV.BA.MVSA] Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2012

33. Distinct roles of Bcl-2 and Bcl-Xl in the apoptosis of human bone marrow mesenchymal stem cells during differentiation

Author

Laurent Lescaudron, Philippe Hulin, Lisa Oliver, François M. Vallette, Philippe Naveilhan, Gwenola Bougras, Erika Hue, Dominique Heymann, Julien Rossignol, Apoptosis and Tumor Progression (CRCINA-ÉQUIPE 9), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN), INSERM UMR 643, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateforme MicroPicell [Nantes], HUE, Erika, and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)

Subjects
Programmed cell death, endocrine system, Cellular differentiation, Science, bcl-X Protein, Bone Marrow Cells, Apoptosis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Bcl-xL, Biology, Mitochondrion, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Molecular Cell Biology, Humans, Cellular Stress Responses, 030304 developmental biology, 0303 health sciences, Multidisciplinary, Cell Death, Stem Cells, Mesenchymal stem cell, Proteins, Mesenchymal Stem Cells, Cell Differentiation, equipment and supplies, Cell biology, Adult Stem Cells, Proto-Oncogene Proteins c-bcl-2, Cytoplasm, 030220 oncology & carcinogenesis, biology.protein, Medicine, Ectopic expression, Cellular Types, Research Article
Abstract

International audience; Background: Adult mesenchymal stem cells (MSCs) can be maintained over extended periods of time before activation and differentiation. Little is known about the programs that sustain the survival of these cells.Principal Findings: Undifferentiated adult human MSCs (hMSCs) did not undergo apoptosis in response to different cell death inducers. Conversely, the same inducers can readily induce apoptosis when hMSCs are engaged in the early stages of differentiation. The survival of undifferentiated cells is linked to the expression of Bcl-Xl and Bcl-2 in completely opposite ways. Bcl-Xl is expressed at similar levels in undifferentiated and differentiated hMSCs while Bcl-2 is expressed only in differentiated cells. In undifferentiated hMSCs, the down-regulation of Bcl-Xl is associated with an increased sensitivity to apoptosis while the ectopic expression of Bcl-2 induced apoptosis. This apoptosis is linked to the presence of cytoplasmic Nur 77 in undifferentiated hMSCs.Significance: In hMSCs, the expression of Bcl-2 depends on cellular differentiation and can be either pro- or anti-apoptotic. Bcl-Xl, on the other hand, exhibits an anti-apoptotic activity under all conditions.

Published
2011
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results