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1. Detection of SARS‐CoV‐2 in two cats during the second wave of the COVID‐19 pandemic in France

Author

Nicolas Nesi, Meriadeg Ar Gouilh, Vincent Legros, Solène Denolly, Eric M. Leroy, Bertrand Boson, Alexandra Briend-Marchal, Serge G. Rosolen, Matthieu Fritz, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Virus enveloppés, vecteurs et immunothérapie – Enveloped viruses, Vectors and Immuno-therapy (EVIR), 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), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Institut de la Vision, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Clinique Vétérinaire Voltaire, Vebiotel - Laboratoire de Biologie Vétérinaire, Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), French National Agency for Research : ANR-RA-COVID-19 (Geographical and temporal serological investigation of companion animal infection with SARS-CoV-2 during the second wave of COVID-19 in France, CoVet), IDEXLYON project of Université de Lyon as part of the 'Programme Investissements d’Avenir'. Grant Number: ANR-16-IDEX-0005, WHO throught the SARS-CoV-2 EvoZoone project, OIE through the European Union EBO-SURSY project, ANR-16-IDEX-0005,IDEXLYON,IDEXLYON(2016), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique et évolution des maladies infectieuses (GEMI), Gestionnaire, HAL Sorbonne Université 5, and IDEXLYON - - IDEXLYON2016 - ANR-16-IDEX-0005 - IDEX - VALID

Subjects
Coronavirus disease 2019 (COVID-19), Veterinary medicine, viruses, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), serology, mild‐respiratory clinical signs, Cat Diseases, SARS‐CoV‐2, Microsphere, Serology, 03 medical and health sciences, SF600-1100, Pandemic, Animals, Medicine, One Health, skin and connective tissue diseases, Pandemics, mild-respiratory clinical signs, 030304 developmental biology, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, CATS, General Veterinary, biology, medicine.diagnostic_test, SARS-CoV-2, 030306 microbiology, business.industry, cats, fungi, [SDV.BA.MVSA] Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, COVID-19, Original Articles, Virology, respiratory tract diseases, 3. Good health, body regions, NGS, Immunoassay, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology.protein, Original Article, France, Antibody, business
Abstract

Although there are several reports in the literature of SARS‐CoV‐2 infection in cats, few SARS‐CoV‐2 sequences from infected cats have been published. In this study, SARS‐CoV‐2 infection was evaluated in two cats by clinical observation, molecular biology (qPCR and NGS), and serology (microsphere immunoassay and seroneutralization). Following the observation of symptomatic SARS‐CoV‐2 infection in two cats, infection status was confirmed by RT‐qPCR and, in one cat, serological analysis for antibodies against N‐protein and S‐protein, as well as neutralizing antibodies. Comparative analysis of five SARS‐CoV‐2 sequence fragments obtained from one of the cats showed that this infection was not with one of the three recently emerged variants of SARS‐CoV‐2. This study provides additional information on the clinical, molecular, and serological aspects of SARS‐CoV‐2 infection in cats., This study provides additional information on the clinical, molecular, and serological aspects of SARS‐CoV‐2 infection in cats.

Published
2021

2. p53 regulates CD46 expression and measles virus infection in myeloma cells

Author

Marion Eveillard, Steven Le Gouill, Laurent Maillet, Catherine Godon, Sophie Barillé-Nion, Marc Grégoire, Martine Amiot, Astrid Vabret, David Chiron, Frédéric Tangy, Jean-François Fonteneau, Philippe Moreau, Benoit Tessoulin, Yannick Le Bris, Anne Lok, Catherine Pellat-Deceunynck, Celine Bellanger, Géraldine Descamps, Agnès Moreau-Aubry, Service d'Hématologie Clinique [CHU Nantes] (Unité d'Investigation Clinique), Centre hospitalier universitaire de Nantes (CHU Nantes), Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), 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), Laboratoire d'Hematologie [CHU de Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Stress Adaptation and Tumor Escape in Breast Cancer (CRCINA-ÉQUIPE 8), Immunogenic Cell Death and Mesothelioma Therapy (CRCINA-ÉQUIPE 4), Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11), Génomique virale et vaccination, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Ligue Régionale Contre le Cancer, DHU Oncogreffe, Actions Cancer 44, L'HémaNexT (i-site NexT), SIRIC ILIAD (INCa-DGOS-Inserm_12558), 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), 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), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), ANR-16-IDEX-0007,NExT (I-SITE),NExT (I-SITE)(2016), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Bernardo, Elizabeth

Subjects
0301 basic medicine, Programmed cell death, viruses, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Membrane Cofactor Protein, Measles virus, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, immune system diseases, RNA interference, hemic and lymphatic diseases, Cell Line, Tumor, microRNA, Gene expression, Humans, Gene silencing, RNA, Small Interfering, Lymphoid Neoplasia, Hematology, biology.organism_classification, Molecular biology, female genital diseases and pregnancy complications, 3. Good health, Oncolytic virus, MicroRNAs, Receptors, TNF-Related Apoptosis-Inducing Ligand, 030104 developmental biology, Cell culture, RNA Interference, Tumor Suppressor Protein p53, Multiple Myeloma, Protein Binding
Abstract

In this study, we assessed the sensitivity of myeloma cells to the oncolytic measles virus (MV) in relation to p53 using 37 cell lines and 23 primary samples. We showed that infection and cell death were correlated with CD46 expression, which was associated with TP53 status; TP53abn cell lines highly expressed CD46 and were preferentially infected by MV when compared with the TP53wt cell lines (P = .046 and P = .045, respectively). Infection of myeloma cells was fully dependent on CD46 expression in both cell lines and primary cells. In the TP53wt cell lines, but not the TP53abn cell lines, activation of the p53 pathway with nutlin3a inhibited both CD46 expression and MV infection, while TP53 silencing reciprocally increased CD46 expression and MV infection. We showed using a p53 chromatin immunoprecipitation assay and microRNA assessment that CD46 gene expression was directly and indirectly regulated by p53. Primary myeloma cells overexpressed CD46 as compared with normal cells and were highly infected and killed by MV. CD46 expression and MV infection were inhibited by nutlin3a in primary p53-competent myeloma cells, but not in p53-deficient myeloma cells, and the latter were highly sensitive to MV infection. In summary, myeloma cells were highly sensitive to MV and infection inhibition by the p53 pathway was abrogated in p53-deficient myeloma cells. These results argue for an MV-based clinical trial for patients with p53 deficiency.

Published
2018

3. Hamster and ferret experimental infection with intranasal low dose of a single strain of SARS-CoV-2

Author

Evelyne Picard-Meyer, Francisco J. Salguero, Meriadeg Ar Gouilh, Séverine Murri, Alexandre Servat, Coralie Pulido, Elodie Monchatre-Leroy, Philippe Marianneau, Sandrine Lesellier, Marine Wasniewski, Johann Vulin, Céline Richomme, Franck Boué, Sandra Lacôte, Laboratoire de la rage et de la faune sauvage de Nancy (LRFSN), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Laboratoire de Lyon [ANSES], Public Health England [London], Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), and Normandie Université (NU)

Subjects
0301 basic medicine, MESH: Cricetinae, Antibodies, Viral, MESH: Ferrets, Serology, Pathogenesis, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Cricetinae, Medicine, MESH: COVID-19, 030212 general & internal medicine, Lung, 0303 health sciences, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, MESH: Real-Time Polymerase Chain Reaction, Brain, virus diseases, Viral Load, respiratory system, Pathophysiology, 3. Good health, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Disease Progression, Positive-strand RNA Viruses, Infection, MESH: Viral Load, Research Article, Hamster, Biology, Nose, Real-Time Polymerase Chain Reaction, Virus, Severity, Excretion, 03 medical and health sciences, Immune system, In vivo, Virology, Animals, Ferret, MESH: SARS-CoV-2, Experimental model, 030304 developmental biology, business.industry, Animal, SARS-CoV-2, Ferrets, COVID-19, Disease Models, Animal, 030104 developmental biology, Immunoglobulin G, Immunology, Nasal administration, MESH: Disease Models, Animal, business, MESH: Antibodies, Viral
Abstract

Understanding the pathogenesis of the SARS-CoV-2 infection is key to developing preventive and therapeutic strategies against COVID-19, in the case of severe illness but also when the disease is mild. The use of appropriate experimental animal models remains central in thein vivoexploration of the physiopathology of infection and antiviral strategies. This study describes SARS-CoV-2 intranasal infection in ferrets and hamsters with low doses of low-passage SARS-CoV-2 clinical French isolate UCN19, describing infection levels, excretion, immune responses and pathological patterns in both animal species. Individual infection with 103p.f.u. SARS-CoV-2 induced a more severe disease in hamsters than in ferrets. Viral RNA was detected in the lungs of hamsters but not of ferrets and in the brain (olfactory bulb and/or medulla oblongata) of both species. Overall, the clinical disease remained mild, with serological responses detected from 7 days and 10 days post-inoculation in hamsters and ferrets respectively. The virus became undetectable and pathology resolved within 14 days. The kinetics and levels of infection can be used in ferrets and hamsters as experimental models for understanding the pathogenicity of SARS-CoV-2, and testing the protective effect of drugs.

Published
2021

4. Anti-GnRH cijepljenje pastuha koji sjemenom izlučuju uzročnika virusnog arteritisa konja - terensko istraživanje

Author

Fabien Miszczak, Marianne Vidament, Stéphane Pronost, Guillaume Fortier, Bénédicte Ferry, Loïc Legrand, Astrid Vabret, Dominik Burger, Labéo Frank Duncombe, Anne-Lyse Laine, LABÉO, Pôle d’analyses et de recherche de Normandie (LABÉO), Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Department of Clinical Veterinary Medicine - Swiss Institute of Equine Medicine - Vetsuisse Faculty, University Hospital of Bern, Institut Français du Cheval et de L'équitation (IFCE), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université de Tours-Institut Français du Cheval et de l'Equitation [Saumur], 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
2. Zero hunger, 030219 obstetrics & reproductive medicine, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, General Veterinary, Equine arteritis virus, 040301 veterinary sciences, stallion, Semen, 04 agricultural and veterinary sciences, equine arteritis virus, anti-GnRH immunization, viral load, testosterone, Biology, Virology, 3. Good health, 0403 veterinary science, Vaccination, 03 medical and health sciences, 0302 clinical medicine, pastuh, virusni arteritis konja, anti-GnRH imunizacija, količina virusa, testosteron
Abstract

Stallions are natural reservoirs of equine arteritis virus (EAV) in their semen, representing a potential source of outbreaks. The carrier-state is testosterone-dependent, and clears spontaneously in 4 to 40% stallions. Reduction of testosterone secretion may be obtained with the anti-GnRH vaccine Equity. In this report, 16 naturally infected stallions excreting EAV in their semen were vaccinated twice with the vaccine EquityTM and monitored irregularly under field conditions for EAV viral load in their semen and plasmatic testosterone concentration. The results are indicated in months (M) after the first vaccine injection. Testosterone concentrations decreased from 1.7 to 0.2 ng/mL (P, Pastusi su prirodni rezervoar uzročnika virusnog arteritisa konja (EAV), koji se izlučuje u sjemenu, te su zbog toga i potencijalni izvor pojave bolesti. Status prenositelja je ovisan o testosteronu i spontano nestaje u 4 do 40 % pastuha. Izlučivanje testosterona moglo bi se smanjiti anti-GnRH cijepljenjem. U ovom je istraživanju 16 prirodno inficiranih pastuha, koji su izlučivali EAV u sjemenu, cijepljeno dva puta cjepivom EquityTM te je u nepravilnim razmacima i u terenskim uvjetima praćena količina virusa u sjemenu i koncentracija testosterona u plazmi. Rezultati su prikazani prema mjesecima (M) poslije prvog cijepljenja. Koncentracija testosterona smanjena je s 1,7 na 0,2 ng/mL (P < 0,002) poslije tri mjeseca. Poslije pet mjeseci količina virusa smanjena je s 3,2 × 109 na 1,1 × 106 RNA kopija/mL sjemena (P < 0,001). Jedan je pastuh uginuo 7 mjeseci nakon prvog cijepljenja. Od trećeg do desetog mjeseca, 12 od 15 pastuha prestalo je izlučivati virus u sjemenu. Od petog do desetog mjeseca, 9 od 15 pastuha imalo je koncentraciju testosterona u plazmi ≥ 0,5 ng/mL, a njih šestero pokazalo je trajno nisku koncentraciju testosterona (≤ 0,3 ng/mL). Od 14 pastuha, od kojih se očekivao oporavak reproduktivne aktivnosti u sljedećoj sezoni rasploda (< M 12), 8 je bilo negativno na EAV i dalo ždrijebe, a 6 nije bilo za rasplod (4 zbog reproduktivne deficijencije i 2 jer su bili pozitivni na EAV). Svi su pastusi bili negativni na EAV poslije 22 mjeseca, s tim da je jedan pastuh nakon 15 mjesci treći put cijepljen. Ovi rezultati pokazuju da bi anti-GnRH cijepljenje moglo pomoći u eradikaciji EAV-a u pastuha, bez osobita utjecaja na reproduktivnu sposobnost većine njih, osim što je u nekih smanjeno izlučivanje testosterone dulje potrajalo.

Published
2020

5. Massive transient damage of the olfactory epithelium associated with infection of sustentacular cells by SARS-CoV-2 in golden Syrian hamsters

Author

Nicolas Meunier, Ronan Le Goffic, Séverine Murri, Sandra Lacôte, Bertrand Bryche, Marine Wasniewski, Philippe Marianneau, Sandrine Lesellier, Alexandre Servat, Evelyne Picard-Meyer, Meriadeg Ar Gouilh, Audrey St Albin, Olivier Rampin, Romain Volmer, Coralie Pulido, Elodie Monchatre-Leroy, Virologie et Immunologie Moléculaires (VIM (UR 0892)), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Université de Caen Normandie (UNICAEN), Normandie Université (NU), Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Laboratoire de la rage et de la faune sauvage de Nancy (LRFSN), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Physiologie de la Nutrition et du Comportement Alimentaire (PNCA (UMR 0914)), Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-AgroParisTech, Agence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du Travail, ANSES, and We would like to thank Pr. Astrid Vabret (head of the Laboratoire de Virology, CHU de CAEN) for BSL3 facilities access and isolates production, Estelle Leperchois (CHU de Caen) for cell production, Latifa Lakhdar (head of the Plateforme d'exp?rimentation animale, Anses - Laboratoire de Lyon), Bruno Da Costa and Christophe Chevalier for their help with handling samples, Bernard Delmas and all members of VIM for helpful discussions, Pierre Adenot for exceptional access to the confocal during the pandemic (MIMA2 platform, https://doi.org/10.15454/1.5572348210007727E12) and Birte Nielsen for her help improving the manuscript. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Subjects
0301 basic medicine, Nasal cavity, Olfactory system, Pathology, viruses, [SDV]Life Sciences [q-bio], Respiratory virus, OE, Olfactory epithelium, Olfaction Disorders, Behavioral Neuroscience, 0302 clinical medicine, skin and connective tissue diseases, 0303 health sciences, Olfactory Bulb, 3. Good health, medicine.anatomical_structure, medicine.symptom, Coronavirus Infections, OSN, Olfactory sensory neuron, medicine.medical_specialty, Central nervous system, Pneumonia, Viral, Immunology, Anosmia, Sensory system, Olfaction, Biology, Olfactory Receptor Neurons, Article, 03 medical and health sciences, Betacoronavirus, Immune system, Olfactory Mucosa, medicine, Animals, Cilia, Pandemics, 030304 developmental biology, SARS, Lamina propria, Mesocricetus, SARS-CoV-2, Endocrine and Autonomic Systems, fungi, COVID-19, biochemical phenomena, metabolism, and nutrition, Olfactory bulb, body regions, 030104 developmental biology, Olfactory epithelium, 030217 neurology & neurosurgery
Abstract

Highlights • SARS-CoV-2 infects massively the olfactory mucosa in hamsters. • SARS-CoV-2 induces desquamation of the olfactory epithelium. • SARS-CoV-2 infects mainly sustentacular cells and not olfactory sensory neurons. • SARS-CoV2 infection lead to a massive recruitment of immune cells. • SARS-CoV-2 was not found in the central nervous system., Anosmia is one of the most prevalent symptoms of SARS-CoV-2 infection during the COVID-19 pandemic. However, the cellular mechanism behind the sudden loss of smell has not yet been investigated. The initial step of odour detection takes place in the pseudostratified olfactory epithelium (OE) mainly composed of olfactory sensory neurons surrounded by supporting cells known as sustentacular cells. The olfactory neurons project their axons to the olfactory bulb in the central nervous system offering a potential pathway for pathogens to enter the central nervous system by bypassing the blood brain barrier. In the present study, we explored the impact of SARS-COV-2 infection on the olfactory system in golden Syrian hamsters. We observed massive damage of the OE as early as 2 days post nasal instillation of SARS-CoV-2, resulting in a major loss of cilia necessary for odour detection. These damages were associated with infection of a large proportion of sustentacular cells but not of olfactory neurons, and we did not detect any presence of the virus in the olfactory bulbs. We observed massive infiltration of immune cells in the OE and lamina propria of infected animals, which may contribute to the desquamation of the OE. The OE was partially restored 14 days post infection. Anosmia observed in COVID-19 patient is therefore likely to be linked to a massive and fast desquamation of the OE following sustentacular cells infection with SARS-CoV-2 and subsequent recruitment of immune cells in the OE and lamina propria.

Published
2020

6. Surveillance of HIV-1 primary infections in France from 2014 to 2016: toward stable resistance, but higher diversity, clustering and virulence?

Author

Visseaux, Benoit, Assoumou, Lambert, Grude, Maxime, Carles, Marie-Josée, Meyer, Laurence, Roussel, Catherine, Le Guillou-Guillemette, H., Ducancelle, A., Courdavault, L, Alloui, C, Honore, P, Lepiller, Q., Bettinger, D., Bellecave, P., Pinson-Recordon, P, Tumiotto, Camille, Vallet, Sophie, Payan, C., Duthe, J, Leroux, M., Dina, Julia, Vabret, A., Mirand, A., Henquell, C., Bouvier-Alias, Magali, Simohamed, A, dos Santos, G, yerly, S, Gaille, C, Caveng, W, Chapalay, S, Calmy, A., Signori-Schmuck, Anne, Morand, Patrice, Pallier, Coralie, Raho-Moussa, M, Mole, M, Dulucq, M-J, Bocket, Laurence, Alidjinou, K, Ranger-Rogez, S, Trabaud, Mary-Anne, Icard, V, Tardy, J., Tamalet, C., Delamare, C, Montes, Brigitte, Schvoerer, E., Fenaux, H., Rodallec, A., André-Garnier, E., Ferre, Virginie, de Monte, Anne, Guigon, A., Guinard, J., Descamps, Diane, Charpentier, C., Peytavin, G., Tremaux, P, Avettand-Fenoel, V., Soulie, C., Malet, I., Wirden, Marc, Marcelin, A, Calvez, V., Flandre, P., Costagliola, D, Morand-Joubert, Laurence, Lambert-Niclot, S., Fofana, D, Boukli, N., Delaugerre, C., Chaix, Marie-Laure, Mahjoub, Nadia, Amiel, Corinne, Giraudeau, G, Beby-Defaux, A., Plainchamp, D, Maillard, Anne, Alessandri-Gradt, E, Leoz, M, Plantier, Jean-Christophe, Gantner, P, Delagreverie, H, Fafi-Kremer, Samira, Fischer, P, Raymond, Stéphanie, Izopet, Jacques, Chiabrando, J, Stefic, Karl, Barin, F., Fajole, G, Burgault, O, Marque-Juillet, S, Service de Virologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB), virology, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre de recherche sur l'hétéroepitaxie et ses applications (CRHEA), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Clermont-Ferrand, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Geneva University Hospital (HUG), Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire de virologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de virologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Hôtel-Dieu de Nantes, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Radiologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Pharmacie de l'Hôpital Bichat, Centre de Recherches Pétrographiques et Géochimiques (CRPG), Institut national des sciences de l'Univers (INSU - CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de Virologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Service de microbiologie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Génétique et Ecologie des Virus, Génétique des Virus et Pathogénèse des Maladies Virales, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Virologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Unité de Rétrovirologie, Hôpital Pontchaillou, Normandie Université (NU), Laboratoire de Virologie, CHU Strasbourg, Laboratoire de Virologie [Toulouse], CHU Toulouse [Toulouse], Service de bactériologie-virologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Centre national de référence du VIH INSERM U966, Université de Tours (UT), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Besançon, Université de Franche-Comté (UFC), Université Grenoble Alpes (UGA), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Unit for Virus Host-Cell Interactions [Grenoble] (UVHCI), Université Joseph Fourier - Grenoble 1 (UJF)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie structurale (IBS - UMR 5075), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU AMU), Stress, Immunité, Pathogènes (SIMPA), Université de Lorraine (UL), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Physiologie, Environnement et Génétique pour l'Animal et les Systèmes d'Elevage [Rennes] (PEGASE), AGROCAMPUS OUEST-Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], CHU Saint-Antoine [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université de Tours, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Service de virologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)

Subjects
Male, Etravirine, HIV Infections, Men who have sex with men, Sexual and Gender Minorities, chemistry.chemical_compound, Pre-exposure prophylaxis, 0302 clinical medicine, Pharmacology (medical), 030212 general & internal medicine, Phylogeny, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, education.field_of_study, Virulence, biology, [SDE.IE]Environmental Sciences/Environmental Engineering, Middle Aged, Viral Load, 3. Good health, Integrase, Infectious Diseases, Rilpivirine, Epidemiological Monitoring, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, France, Viral load, medicine.drug, Adult, Microbiology (medical), Genotype, Anti-HIV Agents, [SDE.MCG]Environmental Sciences/Global Changes, Population, Evolution, Molecular, 03 medical and health sciences, Drug Resistance, Viral, medicine, Humans, education, Pharmacology, 030306 microbiology, Genetic Variation, Sequence Analysis, DNA, [SDE.ES]Environmental Sciences/Environmental and Society, Virology, chemistry, Mutation, HIV-1, biology.protein, [SDE.BE]Environmental Sciences/Biodiversity and Ecology
Abstract

ObjectivesPatients with primary HIV-1 infection (PHI) are a particular population, giving important insight about ongoing evolution of transmitted drug resistance-associated mutation (TDRAM) prevalence, HIV diversity and clustering patterns. We describe these evolutions of PHI patients diagnosed in France from 2014 to 2016.MethodsA total of 1121 PHI patients were included. TDRAMs were characterized using the 2009 Stanford list and the French ANRS algorithm. Viral subtypes and recent transmission clusters (RTCs) were also determined.ResultsPatients were mainly MSM (70%) living in the Paris area (42%). TDRAMs were identified among 10.8% of patients and rose to 18.6% when including etravirine and rilpivirine TDRAMs. Prevalences of PI-, NRTI-, first-generation NNRTI-, second-generation NNRTI- and integrase inhibitor-associated TDRAMs were 2.9%, 5.0%, 4.0%, 9.4% and 5.4%, respectively. In a multivariable analysis, age >40 years and non-R5 tropic viruses were associated with a >2-fold increased risk of TDRAMs. Regarding HIV diversity, subtype B and CRF02_AG (where CRF stands for circulating recombinant form) were the two main lineages (56% and 20%, respectively). CRF02_AG was associated with higher viral load than subtype B (5.83 versus 5.40 log10 copies/mL, P = 0.004). We identified 138 RTCs ranging from 2 to 14 patients and including overall 41% from the global population. Patients in RTCs were younger, more frequently born in France and more frequently MSM.ConclusionsSince 2007, the proportion of TDRAMs has been stable among French PHI patients. Non-B lineages are increasing and may be associated with more virulent CRF02_AG strains. The presence of large RTCs highlights the need for real-time cluster identification to trigger specific prevention action to achieve better control of the epidemic.

Published
2019

7. Sequencing and analysis of globally obtained human parainfluenza viruses 1 and 3 genomes

Author

Martha I. Nelson, Neha Gupta, Paolo Amedeo, Kelly J. Henrickson, Christopher D. Town, Samuel Cordey, Daniel E. Noyola, Cristina Videla, Susmita Shrivastava, Tuckweng Kok, Astrid Vabret, Rebecca A. Halpin, Michael E. Bose, Nadia Fedorova, Hernan Lorenzi, Marietjie Venter, Amelia Buys, Jie He, Jayati Bera, Medical College of Wisconsin [Milwaukee] (MCW), J. Craig Venter Institute, Fogarty International Center, National Institutes of Health [Bethesda] (NIH), Universidad Autonoma de San Luis Potosi [México] (UASLP), Centro de Educación Médica e Investigaciones Clínicas (CEMIC), University of South Australia [Adelaide], National Institute for Communicable Diseases [Johannesburg] (NICD), University of Pretoria [South Africa], Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), and Geneva University Hospital (HUG)

Subjects
RNA viruses, 0301 basic medicine, medicine.disease_cause, Genome, Database and Informatics Methods, Influenza A virus, Genome Evolution, Phylogeny, Pathology and laboratory medicine, ComputingMilieux_MISCELLANEOUS, Data Management, ddc:616, Recombination, Genetic, Genetics, Multidisciplinary, High-Throughput Nucleotide Sequencing, Phylogenetic Analysis, Genomics, Medical microbiology, 3. Good health, Phylogenetics, Human Parainfluenza Virus, Viruses, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Evolutionary Rate, Medicine, Pathogens, Sequence Analysis, Research Article, Computer and Information Sciences, Evolutionary Processes, Bioinformatics, Sequence analysis, Science, 030106 microbiology, Genome, Viral, Biology, Research and Analysis Methods, Microbiology, Molecular Evolution, Virus, Evolution, Molecular, 03 medical and health sciences, Sequence Motif Analysis, medicine, Humans, Influenza viruses, Evolutionary Systematics, Parainfluenza Virus 1, Human/genetics, Selection, Genetic, Taxonomy, Medicine and health sciences, Evolutionary Biology, Sequence Assembly Tools, Organisms, Viral pathogens, Biology and Life Sciences, Computational Biology, Sequence Analysis, DNA, Ion semiconductor sequencing, Genome Analysis, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Genomics/methods, Parainfluenza Virus 1, Human, Parainfluenza Virus 3, Human, Microbial pathogens, 030104 developmental biology, Parainfluenza Virus 3, Human/genetics, Sequence Alignment, Orthomyxoviruses
Abstract

Human Parainfluenza viruses (HPIV) type 1 and 3 are important causes of respiratory tract infections in young children globally. HPIV infections do not confer complete protective immunity so reinfections occur throughout life. Since no effective vaccine is available for the two virus subtypes, comprehensive understanding of HPIV-1 and HPIV-3 genetic and epidemic features is important for diagnosis, prevention, and treatment of HPIV-1 and HPIV-3 infections. Relatively few whole genome sequences are available for both HPIV-1 and HPIV-3 viruses, so our study sought to provide whole genome sequences from multiple countries to further the understanding of the global diversity of HPIV at a whole-genome level. We collected HPIV-1 and HPIV-3 samples and isolates from Argentina, Australia, France, Mexico, South Africa, Switzerland, and USA from the years 2003-2011 and sequenced the genomes of 40 HPIV-1 and 75 HPIV-3 viruses with Sanger and next-generation sequencing with the Ion Torrent, Illumina, and 454 platforms. Phylogenetic analysis showed that the HPIV-1 genome is evolving at an estimated rate of 4.97 × 10-4 mutations/site/year (95% highest posterior density 4.55 × 10-4 to 5.38 × 10-4) and the HPIV-3 genome is evolving at a similar rate (3.59 × 10-4 mutations/site/year, 95% highest posterior density 3.26 × 10-4 to 3.94 × 10-4). There were multiple genetically distinct lineages of both HPIV-1 and 3 circulating on a global scale. Further surveillance and whole-genome sequencing are greatly needed to better understand the spatial dynamics of these important respiratory viruses in humans.

Published
2019

8. Resistance to integrase inhibitors: a national study in HIV-1-infected treatment-naive and -experienced patients

Author

Constance Delaugerre, Virginie Ferré, Anne Maillard, Vincent Calvez, Audrey Mirand, Anne-Geneviève Marcelin, Corinne Amiel, Julia Dina, Coralie Pallier, Hélène Le Guillou-Guillemette, Stéphanie Raymond, D. B. Fofana, Thomas Mourez, Hélène Jeulin, Samira Fafi-Kremer, Brigitte Montes, Pantxika Bellecave, Sophie Vallet, Thuy Van Nguyen, Diane Descamps, Catherine Roussel, Maxime Grude, Mary-Anne Trabaud, Charlotte Charpentier, Laurence Bocket, Philippe Flandre, Laura Le Guen, Anne Signori-Schmuck, Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Toulouse [Toulouse], Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), CIC CHU ( Lille)/inserm, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Laboratoire de Virologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Simulation et Traitement de l'information pour l'Exploitation des systèmes de Production (EDF R&D STEP), EDF R&D (EDF R&D), EDF (EDF)-EDF (EDF), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Laboratoire de virologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Interaction virus-hôte et maladies du foie, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Amiens-Picardie, Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [Rennes] = Virology [Rennes], CHU Pontchaillou [Rennes], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Microbiologie Fondamentale et Pathogénicité (MFP), Service de virologie et unité de surveillance biologique [Bordeaux], CHU Bordeaux [Bordeaux], Hôpital Paul Brousse, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Clermont-Ferrand, CHU Lille, CHU Saint-Antoine [AP-HP], Laboratoire de Virologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Hôpital Saint Eloi (CHRU Montpellier), Service de Virologie [CHRU Nancy], CHU Strasbourg, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université de Caen Normandie (UNICAEN), Service de Virologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Université Sorbonne Paris Nord, Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [Toulouse], CHU Saint-Eloi, Mzembaba, Sandy, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Male, 0301 basic medicine, MESH: Sequence Analysis, DNA, MESH: Treatment Failure, Aucun, Integrase inhibitor, HIV Infections, Drug resistance, MESH: HIV Seropositivity / drug therapy, MESH: Genotype, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, HIV Seropositivity, Pharmacology (medical), Treatment Failure, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Middle Aged, biology, Elvitegravir, Middle Aged, Viral Load, 3. Good health, Integrase, MESH: HIV-1 / genetics, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Dolutegravir, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, Viral load, medicine.drug, Adult, Microbiology (medical), medicine.medical_specialty, MESH: Mutation, Genotype, MESH: HIV Integrase Inhibitors / therapeutic use, 030106 microbiology, MESH: HIV Infections / drug therapy, MESH: Drug Resistance, Multiple, Viral / genetics, MESH: HIV-1 / drug effects, 03 medical and health sciences, Drug Resistance, Multiple, Viral, Internal medicine, medicine, Humans, HIV Integrase Inhibitors, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Pharmacology, MESH: Viral Load / drug effects, MESH: Humans, business.industry, MESH: Adult, Sequence Analysis, DNA, Raltegravir, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Male, Regimen, chemistry, Mutation, HIV-1, biology.protein, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business, MESH: Female
Abstract

International audience; Objectives: To describe integrase strand transfer inhibitor (INSTI) resistance profiles and factors associated with resistance in antiretroviral-naive and -experienced patients failing an INSTI-based regimen in clinical practice.Methods: Data were collected from patients failing an INSTI-containing regimen in a multicentre French study between 2014 and 2017. Failure was defined as two consecutive plasma viral loads (VL) >50 copies/mL. Reverse transcriptase, protease and integrase coding regions were sequenced at baseline and failure. INSTI resistance-associated mutations (RAMs) included in the Agence Nationale de Recherches sur le SIDA genotypic algorithm were investigated.Results: Among the 674 patients, 359 were failing on raltegravir, 154 on elvitegravir and 161 on dolutegravir therapy. Overall, 90% were experienced patients and 389 (58%) patients showed no INSTI RAMs at failure. The strongest factors associated with emergence of at least one INSTI mutation were high VL at failure (OR = 1.2 per 1 log10 copies/mL increase) and low genotypic sensitivity score (GSS) (OR = 0.08 for GSS ≥3 versus GSS = 0-0.5). Patients failing dolutegravir also had significantly fewer INSTI RAMs at failure than patients failing raltegravir (OR = 0.57, P = 0.02) or elvitegravir (OR = 0.45, P = 0.005). Among the 68 patients failing a first-line regimen, 11/41 (27%) patients on raltegravir, 7/18 (39%) on elvitegravir and 0/9 on dolutegravir had viruses with emergent INSTI RAMs at failure.Conclusions: These results confirmed the robustness of dolutegravir regarding resistance selection in integrase in the case of virological failure in routine clinical care.

Published
2019

9. Phylogenetic variability of Human Metapneumovirus in patients with acute respiratory infections in Cameroon, 2011–2014

Author

Richard Njouom, Sebastien Kenmoe, Marie-Astrid Vernet, Véronique Penlap Beng, Astrid Vabret, Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Université de Yaoundé I, Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), and This work was funded by the U.S. Department of Health and Human Services (DHHS) grant number 6 DESP060001-01-01 via the International Network of Pasteur Institutes and the ‘Institut de Microbiologie et de Maladies Infectieuses’ (IMMI) in France.

Subjects
0301 basic medicine, Male, viruses, Polymerase Chain Reaction, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Genotype, 030212 general & internal medicine, Cameroon, Child, Respiratory Tract Infections, Phylogeny, Paramyxoviridae Infections, biology, Phylogenetic tree, Sub-Saharan Africa, lcsh:Public aspects of medicine, virus diseases, General Medicine, Pneumovirus, 3. Good health, Infectious Diseases, Child, Preschool, Acute Disease, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Respiratory virus, Female, Acute respiratory infections, Adolescent, 030106 microbiology, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Human metapneumovirus, Multiplex polymerase chain reaction, Humans, lcsh:RC109-216, Genetic variability, Molecular epidemiology, Public Health, Environmental and Occupational Health, Infant, Newborn, Genetic Variation, Infant, lcsh:RA1-1270, biology.organism_classification, Virology, Human Metapneumovirus, respiratory tract diseases, Metapneumovirus
Abstract

Background: Identified in 2001, Human Metapneumovirus (HMPV) is a Pneumovirus associated with acute lower and upper respiratory infections in all age groups and especially in newborns, elderly and immunocompromised subjects. Data are still limited in sub-Saharan African countries genetic characterization of this respiratory virus. This study reports the genetic variability of HMPV strains in Cameroonian children for 3 consecutive epidemic seasons (September 2011–October 2014). Methods: A prospective surveillance was conducted to identify inpatient and outpatient children less than 15 years with respiratory symptoms ≤5 days. The nasopharyngeal samples were tested for HMPV using a multiplex polymerase chain reaction. Viral distribution and demographic data were analyzed statistically. Positive samples for HMPV were amplified by semi-nested polymerize chain reaction and then partially sequenced at the G gene. Phylogenetic analyzes were performed on the partial nucleotide and protein sequences of the G gene. Results: From September 2011 to October 2014, 822 children under 15 years were enrolled in the study. HMPV was identified in each of 3.9% (32/822) of children. HMPV were detected throughout the year. HMPV-A (73.3%; 11/15) was predominant compared to HMPV-B (26.7; 4/15). Cameroonian HMPV strains are grouped among the members of genotype A2b (for HMPV-A), B1 and B2 (for HMPV-B). Conclusion: This study suggests that about 4% of ARI recorded in children in Cameroon are caused by HMPV. The present study is also the first report on the genetic variability of the G gene of HMPV strains in the region. Although this work partially fills gaps for some information, additional studies are required to clarify the molecular epidemiology and evolutionary pattern of HMPV in sub-Saharan Africa in general and more particularly in Cameroon. Keywords: Acute respiratory infections, Human Metapneumovirus, Genetic variability, Sub-Saharan Africa, Cameroon

Published
2019

10. Comparative performance of the Biocentric Generic Viral Load, Roche CAP/CTM v1.5, Roche CAP/CTM v2.0 and m2000 Abbott assays for quantifying HIV-1 B and non-B strains: Underestimation of some CRF02 strains

Author

M Gousset, Adeline Mélard, Marie Gueudin, Marie-Laure Chaix, Laurence Meyer, N. Lerolle, Julia Dina, Jean-Paul Viard, Jean-Christophe Plantier, Véronique Avettand-Fenoel, Christine Rouzioux, Anne Maillard, Laboratoire de Virologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Laboratoire de virologie [Rouen], CHU Rouen, Laboratoire de Virologie CHU de Rennes, Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Laboratoire de Virologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre de recherche en épidémiologie et santé des populations (CESP), Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV) (EA 7327), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Laboratoire de Virologie [Rennes] = Virology [Rennes], CHU Pontchaillou [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)

Subjects
0301 basic medicine, 030106 microbiology, Human immunodeficiency virus (HIV), HIV Infections, Biology, medicine.disease_cause, Sensitivity and Specificity, World health, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Genetic Evolution, Virology, HIV Seropositivity, medicine, Humans, Mass Screening, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Plasma samples, Clinical Laboratory Techniques, Viral Load, Antiretroviral therapy, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Epidemiological surveillance, HIV-1, RNA, Viral, France, Viral load
Abstract

Background HIV-1 viral load testing is now recommended by the World Health Organization for every patient receiving antiretroviral therapy (ART). Objectives The objective of this study is to evaluate the performance of commercial assays for their ability to quantify HIV-1 strains currently circulating in France. Study design The performances of the Generic HIV-RNA assay from Biocentric were compared to those of the Roche CAP/CTM v1.5, Roche CAP/CTM v2.0 and Abbott m2000 RealTime HIV-1 assays. A total of 1885 HIV-1 plasma samples were tested, including 684 samples from patients included in the ANRS-Primo Cohort. Results We found a good concordance of quantification between the Roche v2.0 and the Biocentric assays, both of which were superior to the Roche v1.5 assay. We show moderate agreement between techniques; however, CRF02_AG strains and undetermined viruses were underestimated when quantified with the Roche CAP/CTM v2.0. In contrast, a comparison of the Biocentric and Abbott assay results showed strong agreement between assays, indicating that both are well suited for quantification of CRF02_AG strains. Moreover, a 2% underestimation of the B subtypes was observed with the Biocentric assay. Conclusions These results have implications for viral load monitoring in Western Africa, where CRF02_AG strains are highly prevalent. Closer epidemiological surveillance and evaluation of commercial assays are still necessary to better evaluate the impact of the genetic evolution of circulating viruses on HIV-RNA quantification in the regions most affected by the HIV-1 epidemic.

Published
2019

11. Measles inclusion-body encephalitis (MIBE) in a immunocompromised patient

Author

Arnaud de La Blanchardière, A. Baldolli, Erick Cardineau, Sylvie Dargère, Astrid Vabret, Renaud Verdon, Julia Dina, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Intercommunal Alençon-Mamers (CHICAM), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Service de Virologie [CHU Caen], Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Unité de Maladies Infectieuses et Tropicales [CHU Caen], and Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN)

Subjects
Adult, 0301 basic medicine, Fatal outcome, Microscopic Polyangiitis, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Measles, Subacute sclerosing panencephalitis, Measles virus, Immunocompromised Host, 03 medical and health sciences, Fatal Outcome, 0302 clinical medicine, Virology, medicine, Humans, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, biology, business.industry, Immunocompromised patient, biology.organism_classification, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 030104 developmental biology, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, Subacute Sclerosing Panencephalitis, Measles Inclusion Body Encephalitis, Microscopic polyangiitis, business
Abstract

International audience

Published
2016

12. Phenotypic analysis of HIV-1 E157Q integrase polymorphism and impact on virological outcome in patients initiating an integrase inhibitor-based regimen

Author

Alexandre Storto, Diane Descamps, Anne Maillard, Audrey Mirand, Corinne Amiel, Charlotte Charpentier, Vincent Calvez, Thuy Van Nguyen, Laurence Bocket, Coralie Pallier, Audrey Rodallec, Elisabeth André-Garnier, Marie Leoz, Laurence Morand-Joubert, Isabelle Malet, Stéphanie Raymond, Véronique Schneider, Catherine Roussel, Camille Tumiotto, Constance Delaugerre, Anne-Geneviève Marcelin, Julia Dina, Jean-Christophe Plantier, Brigitte Montes, Anne Signori-Schmuck, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Université Paris Diderot - Paris 7 (UPD7), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôtel-Dieu de Nantes, Service de Virologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de bactériologie-virologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de virologie [Hôpital Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Ecophysiologie Végétale, Agronomie et Nutritions (EVA), Institut National de la Recherche Agronomique (INRA)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Service de virologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire de virologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Virologie [Villejuif], Hôpital Paul Brousse, Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Service de bactériologie-virologie [Tours], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [Toulouse], CHU Toulouse [Toulouse], Génétique et Ecologie des Virus, Génétique des Virus et Pathogénèse des Maladies Virales, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Virologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], CHU Tenon [APHP], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Recherche Agronomique (INRA), Laboratoire Microorganismes : Génome et Environnement - Clermont Auvergne (LMGE), Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Unit for Virus Host-Cell Interactions [Grenoble] (UVHCI), Université Joseph Fourier - Grenoble 1 (UJF)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)

Subjects
0301 basic medicine, Microbiology (medical), Genotype, 030106 microbiology, Mutation, Missense, Integrase inhibitor, HIV Infections, HIV Integrase, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Virus, 03 medical and health sciences, chemistry.chemical_compound, Gene Frequency, medicine, Prevalence, Humans, Pharmacology (medical), HIV Integrase Inhibitors, Pharmacology, biology, Elvitegravir, business.industry, Viral Load, Raltegravir, Virology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Integrase, Regimen, Infectious Diseases, Treatment Outcome, chemistry, Dolutegravir, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology.protein, HIV-1, France, business, Viral load, medicine.drug
Abstract

International audience; ObjectivesTo assess the phenotypic susceptibility of the E157Q polymorphism in HIV-1 integrase (IN) and the virological outcome of patients infected with E157Q-mutated virus initiating an IN inhibitor (INI)-based regimen.MethodsThis was a multicentre study assessing IN sequences from INI-naive patients among 17 French HIV clinical centres. E157Q site-directed mutants in pNL4.3 and pCRF02_AG contexts were assessed in a recombinant phenotypic assay.ResultsPrevalence of the E157Q polymorphism was 2.7% among 8528 IN sequences from INI-naive patients and its distribution was 1.7%, 5.6% and 2.2% in B, CRF02_AG and various non-B subtypes, respectively. Thirty-nine INI-naive patients with E157Q-mutated virus initiated an INI-based regimen. Among them, 15 had a viral load (VL) 50 copies/mL at the time of INI-based regimen initiation. Among them eight were receiving a first-line regimen and the only two patients who did not reach VL

Published
2018

13. Molecular characterization of human adenovirus associated with acute respiratory infections in Cameroon from 2011 to 2014

Author

Marie-Astrid Vernet, Astrid Vabret, Jérôme Le Goff, Veronique Penlap, Richard Njouom, Sebastien Kenmoe, Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), Université de Yaoundé I, Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), and This work was funded by the U.S. Department of Health and Human Services (DHHS) grant number 6 DESP060001–01-01 via the International Network of Pasteur Institutes and the ‘Institut de Microbiologie et de Maladies Infectieuses’ (IMMI) in France.

Subjects
Male, 0301 basic medicine, Human Adenoviruses, Adolescent, Genotype, Genotyping Techniques, Adenoviridae Infections, Biology, Real-Time Polymerase Chain Reaction, Demographic data, Virus, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Nasopharynx, Virology, Humans, lcsh:RC109-216, Cameroon, Respiratory system, Child, Respiratory Tract Infections, Phylogeny, Molecular Epidemiology, Molecular epidemiology, Phylogenetic tree, Adenoviruses, Human, Research, Infant, Newborn, Human adenovirus, Genetic Variation, Infant, virus diseases, Sequence Analysis, DNA, biology.organism_classification, Hexon gene, eye diseases, Molecular characterization, 3. Good health, Hospitalization, Mastadenovirus, 030104 developmental biology, Infectious Diseases, Child, Preschool, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract

International audience; BACKGROUND: Human adenoviruses (HAdVs) cause a wide range of diseases worldwide, including respiratory infections. Studies on HAdV molecular epidemiology are limited in Cameroon. The purpose of this study is to document the different types HAdV circulating in Cameroon in children with acute respiratory infections.METHODS: Nasopharyngeal swabs were collected from 811 children under 15 years from 2011 to 2014. The HAdV detection was assessed by semi-quantitative generic PCR r-gene®. The HAdV-positive samples were typed by amplification and sequencing of partial hexon gene and a real-time PCR. Demographic data were collected and analyzed. The infection and hospitalization risk factors were assessed thought the Chi-square test.RESULTS: A total of 137/220 HAdV-positive samples were amplified successfully. Six species of HAdV (Mastadenovirus A to F) were detected with B (108/220) and C (47/220) being the predominant strains. Hospitalization and age were significantly associated to HAdV-B and HAdV-C respectively. Phylogenetic analysis of HAdV-B3 virus (18) and B7 (5) shows a conserved and a significant temporal stability in relation to the reference sequence (99.1 to 100% of similarity).CONCLUSION: This study reported HAdV species and types detected in children with acute respiratory infections in Cameroon between September 2011 and July 2014. These results support further evaluation of the spatio-temporal circulation pattern of HAdV species and types in Cameroon.

Published
2018

14. Single reaction, real time RT-PCR detection of all known avian and human metapneumoviruses

Author

Paul A. Brown, Astrid Vabret, Chantal Allee, E Lemaitre, Nicolas Eterradossi, Université européenne de Bretagne - European University of Brittany (UEB), Avian and Rabbit Virology Immmunology and Parasitology Reserach Unit (VIPAC), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Service de Virologie [CHU Caen], CHU Caen, and Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)

Subjects
0301 basic medicine, animal structures, Time Factors, 040301 veterinary sciences, Diamines, Real-Time Polymerase Chain Reaction, Genome, Sensitivity and Specificity, Article, law.invention, 0403 veterinary science, Birds, 03 medical and health sciences, chemistry.chemical_compound, Human metapneumovirus, law, Virology, Animals, Humans, Metapneumovirus, Avian metapneumovirus, Benzothiazoles, Organic Chemicals, Polymerase chain reaction, Virus classification, ComputingMilieux_MISCELLANEOUS, Genetics, biology, Staining and Labeling, Reverse Transcriptase Polymerase Chain Reaction, virus diseases, 04 agricultural and veterinary sciences, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Real-time RT-PCR, 030104 developmental biology, Real-time polymerase chain reaction, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, chemistry, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, SYBR Green I, Quinolines, Primer (molecular biology)
Abstract

Highlights • Detection of all known avian and human MPV subgroups in a single reaction rRT-PCR. • Highly sensitive and specific method using SYBR Green I technology. • Complete validation of the method for detection of avian metapneumoviruses., Current molecular methods for the detection of avian and human metapneumovirus (AMPV, HMPV) are specifically targeted towards each virus species or individual subgroups of these. Here a broad range SYBR Green I real time RT-PCR was developed which amplified a highly conserved fragment of sequence in the N open reading frame. This method was sufficiently efficient and specific in detecting all MPVs. Its validation according to the NF U47-600 norm for the four AMPV subgroups estimated low limits of detection between 1000 and 10 copies/μL, similar with detection levels described previously for real time RT-PCRs targeting specific subgroups. RNA viruses present a challenge for the design of durable molecular diagnostic test due to the rate of change in their genome sequences which can vary substantially in different areas and over time. The fact that the regions of sequence for primer hybridization in the described method have remained sufficiently conserved since the AMPV and HMPV diverged, should give the best chance of continued detection of current subgroups and of potential unknown or future emerging MPV strains.

Published
2018

15. Genetic diversity of human respiratory syncytial virus isolated among children with acute respiratory infections in Southern Cameroon during three consecutive epidemic seasons, 2011–2013

Author

Richard Njouom, Matthieu Schoenhals, Marie-Astrid Vernet, Véronique Penlap Beng, Fabien Miszczak, Sebastien Kenmoe, Astrid Vabret, Julia Dina, Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Université de Yaoundé I, Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), and This work was funded by the US Department of Health and Human Services (DHHS) grant number 6 DESP060001-01-01 via the International Network of Pasteur Institutes and the 'Institut de Microbiologie et de Maladies Infectieuses' (IMMI) in France.

Subjects
0301 basic medicine, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, Population, Biology, Group B, Virus, 03 medical and health sciences, Genotype, Human respiratory syncytial virus, Genetic variability, Cameroon, education, education.field_of_study, Genetic diversity, Molecular epidemiology, Research, Public Health, Environmental and Occupational Health, Virology, 3. Good health, Hypervariable region, 030104 developmental biology, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Genetic characterization
Abstract

International audience; Background: Human respiratory syncytial virus (HRSV) is the main viral cause of severe lower respiratory tract disease in infants and young children. The aim of this study was to describe for the first time the genetic variability of HRSV in Cameroonian patients living in Yaounde for three consecutive epidemic seasons.Methods: HRSV-positive nasopharyngeal samples detected in children less than 15 years in Yaounde were collected from September 2011 to December 2013. Semi-nested RT-PCR, sequencing, and phylogenetic analyses of the second hypervariable region of the G gene were performed.Results: A total of 57 HRSV-positive samples were collected during the study period. Among these, 46 (80.7%) could be amplified in the G gene. HRSV group A (HRSV-A) and group B (HRSV-B) co-circulated in this population at 17.4 and 82.6%, respectively. HRSV-A strains clustered in the NA-1 genotype while HRSV-B strains clustered in the BA-9 genotype. HRSV-A strains accounted for 33.3% (2/6), 4.3% (1/23), and 29.4% (5/17) of the viruses isolated in 2011, 2012, and 2013, respectively.Conclusions: This study reports molecular epidemiology data of HRSV in Cameroon for the first time. Additional studies are required to clarify evolutionary patterns of HRSV throughout sub-Saharan Africa to support antiviral and vaccine development.

Published
2018

16. Complete Genome Sequence of a Wild-Type Measles Virus Isolated during a 2016 Winter Outbreak in a Refugee Settlement in Calais, France

Author

Denise Antona, Astrid Vabret, Julia Dina, Justine Hamel, Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), and Santé publique France - French National Public Health Agency [Saint-Maurice, France]

Subjects
0301 basic medicine, Refugee, 030106 microbiology, Measles, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Measles virus, 03 medical and health sciences, Genetics, medicine, Molecular Biology, ComputingMilieux_MISCELLANEOUS, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Whole genome sequencing, biology, Outbreak, Calais, biology.organism_classification, medicine.disease, Virology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, 030104 developmental biology, Vaccination coverage, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Viruses, Settlement (litigation)
Abstract

Measles outbreaks are regularly reported in European countries despite efforts to improve vaccination coverage. In January 2016, an outbreak occurred in a refugee settlement in Calais, France. We report here the complete genome sequence of a wild-type measles virus isolated from a health care worker (MVi/Calais. FRA/01.16) infected during this outbreak.

Published
2017

17. Phylogenic analysis of human bocavirus detected in children with acute respiratory infection in Yaounde, Cameroon

Author

Astrid Vabret, Sebastien Kenmoe, Marie-Astrid Vernet, Mohamadou Njankouo-Ripa, Veronique Penlap, Richard Njouom, Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), Université de Yaoundé I, Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), This work was supported by the U.S. Department of Health and Human Services (DHHS) Grant Number 6 DESP060001-01-01 via the International Network of Pasteur Institutes and the ‘Institut de Microbiologie et de Maladies Infectieuses’ (IMMI) in France., and We thank all laboratory and hospital staff involved data and respiratory samples collection used for this study and Dr. Matthieu Schoenhals for his assistance with the English language.

Subjects
0301 basic medicine, lcsh:Medicine, MESH: Parvoviridae Infections/virology, MESH: Human bocavirus/pathogenicity, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Human bocavirus, MESH: Parvoviridae Infections/epidemiology, MESH: Child, Genotype, MESH: Human bocavirus/classification, Medicine, Cameroon, Clade, Child, MESH: Phylogeny, Respiratory Tract Infections, lcsh:QH301-705.5, Children, Phylogeny, Phylogenetic tree, Respiratory tract infections, biology, Respiratory infection, General Medicine, MESH: Respiratory Tract Infections/epidemiology, MESH: Human bocavirus/genetics, 3. Good health, Research Note, Acute respiratory infection, Acute Disease, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Acute Disease, MESH: Cameroon/epidemiology, Parvoviridae Infections, General Biochemistry, Genetics and Molecular Biology, Virus, 03 medical and health sciences, parasitic diseases, Humans, lcsh:Science (General), [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, MESH: Humans, business.industry, lcsh:R, biology.organism_classification, Virology, 030104 developmental biology, lcsh:Biology (General), Africa, business, MESH: Respiratory Tract Infections/virology, lcsh:Q1-390
Abstract

International audience; OBJECTIVE: Human Bocavirus (HBoV) was first identified in 2005 and has been shown to be a common cause of respiratory infections and gastroenteritis in children. In a recent study, we found that 10.7% of children with acute respiratory infections (ARI) were infected by HBoV. Genetic characterization of this virus remains unknown in Central Africa, particularly in Cameroon Leeding us to evaluate the molecular characteristics of HBoV strains in Cameroonian children with ARI.RESULTS: Phylogenetic analysis of partial HBoV VP1/2 sequences showed a low level of nucleotide variation and the circulation of HBoV genotype 1 (HBoV-1) only. Three clades were obtained, two clustering with each of the reference strains ST1 and ST2, and a third group consisting of only Cameroon strains. By comparing with the Swedish reference sequences, ST1 and ST2, Cameroon sequences showed nucleotide and amino acid similarities of respectively 97.36-100% and 98.35-100%. These results could help improve strategies for monitoring and control of respiratory infections in Cameroon.

Published
2017

18. Performance Evaluation of the VIDAS® Measles IgG Assay and Its Diagnostic Value for Measuring IgG Antibody Avidity in Measles Virus Infection

Author

Amelie Hebert, Christian Creveuil, Florent Viron, François Freymuth, Astrid Vabret, Julia Dina, Stéphanie Gouarin, Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Unité de Biostatistique et de Recherche Clinique (UBRC), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, and Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)

Subjects
Male, 0301 basic medicine, Antibody Affinity, lcsh:QR1-502, measles virus, measles diagnosis, measles avidity, Antibodies, Viral, lcsh:Microbiology, Serology, 0302 clinical medicine, Medicine, 030212 general & internal medicine, Child, ComputingMilieux_MISCELLANEOUS, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Aged, 80 and over, Immunoassay, biology, Middle Aged, 3. Good health, Infectious Diseases, Child, Preschool, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, Antibody, Adult, Adolescent, 030106 microbiology, chemical and pharmacologic phenomena, Sensitivity and Specificity, Measles, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Article, Virus, Measles virus, Young Adult, 03 medical and health sciences, Immunity, Virology, Humans, Avidity, Aged, business.industry, Infant, Igg avidity, medicine.disease, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Immunoglobulin G, Immunology, biology.protein, business
Abstract

The objective of this study is primarily to compare the performance of the VIDAS(®) Measles immunoglobulin (Ig)G assay to that of two other serological assays using an immunoassay technique, Enzygnost(®) Anti-measles Virus/IgG (Siemens) and Measles IgG CAPTURE EIA(®) (Microimmune). The sensitivity and the agreement of the VIDAS(®) Measles IgG assay compared to the Enzygnost(®) Anti-measles Virus/IgG assay and the Measles IgG CAPTURE EIA(®) assay are 100%, 97.2% and 99.0%, 98.4%, respectively. The very low number of negative sera for IgG antibodies does not allow calculation of specificity. As a secondary objective, we have evaluated the ability of the VIDAS(®) Measles IgG assay to measure anti-measles virus IgG antibody avidity with the help of the VIDAS(®) CMV IgG Avidity reagent, using 76 sera from subjects with measles and 238 other sera. Different groups of populations were analyzed. In the primary infection measles group, the mean IgG avidity index was 0.16 (range of 0.07 to 0.93) compared to 0.79 (range of 0.25 to 1) in the serum group positive for IgG antibodies and negative for IgM. These data allow to define a weak anti-measles virus IgG antibody avidity as an avidity index (AI)0.3 and a strong avidity as an AI0.6. The VIDAS(®) Measles IgG assay has a performance equivalent to that of other available products. Its use, individual and quick, is well adapted to testing for anti-measles immunity in exposed subjects.

Published
2016

19. Comparative molecular epidemiology of two closely related coronaviruses, bovine coronavirus (BCoV) and human coronavirus OC43 (HCoV-OC43), reveals a different evolutionary pattern

Author

François Moutou, Meriadeg Ar Gouilh, Laure Diancourt, Fabien Miszczak, Valérie Caro, Astrid Vabret, Nathalie Kin, Normandie Université (NU), Unité de Recherche Risques Microbiens (U2RM), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Environnement et Risques infectieux - Environment and Infectious Risks (ERI), Institut Pasteur [Paris], Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), This work was supported by the French Agence Nationale de la Recherche (ANR) on the behalf of EPICOREM project (Eco-Epidemiology of Coronaviruses, from Wildlife to Human: Emergence Threat Assessment), grant ANR-13-BSV3-0013., We are grateful to Stephane Pronost of departmental laboratory LABEO Franck Duncombe of Calvados and to Victor Carpinshi, Fabienne Benoît, and Delphine Esperet of departmental laboratory of Manche, for providing us the field samples. We thank all of our partners of the EPICOREM Consortium., ANR-13-BSV3-0013,EPICOREM,Ecoepidémiologie des coronavirus, de la faune sauvage à l'homme, et risque d'émergence.(2013), and Institut Pasteur [Paris] (IP)

Subjects
0301 basic medicine, MESH: Sequence Analysis, DNA, Genes, Viral, Epidemiology, medicine.disease_cause, Coronavirus OC43, Human, MESH: Genotype, Bovine coronavirus, Respiratory infection, MESH: Computational Biology/methods, Human coronavirus OC43, MESH: Animals, MESH: Coronavirus/classification, MESH: Phylogeny, Phylogeny, MESH: Evolution, Molecular, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Coronavirus, Coronavirus, Bovine, Recombination, Genetic, Genetics, Molecular Epidemiology, MESH: Genes, Viral, Phylogenetic tree, biology, MESH: Molecular Typing, virus diseases, 3. Good health, MESH: Coronavirus Infections/virology, MESH: Cattle, Infectious Diseases, MESH: RNA, Viral, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, RNA, Viral, MESH: Recombination, Genetic, France, MESH: Genome, Viral, Coronavirus Infections, Microbiology (medical), Genotyping, Genotype, Evolution, 030106 microbiology, MESH: Coronavirus Infections/epidemiology, Genome, Viral, Microbiology, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Article, Evolution, Molecular, 03 medical and health sciences, Phylogenetics, MESH: Coronavirus/genetics, medicine, Animals, Humans, MESH: Molecular Epidemiology, Molecular Biology, Ecology, Evolution, Behavior and Systematics, MESH: Humans, Molecular epidemiology, Computational Biology, MESH: Coronavirus OC43, Human/classification, Sequence Analysis, DNA, biology.organism_classification, Virology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Recombination, MESH: Coronavirus OC43, Human/genetics, Molecular Typing, MESH: France, 030104 developmental biology, MESH: Coronavirus, Bovine/genetics, Cattle, MESH: Coronavirus, Bovine/classification
Abstract

Bovine coronaviruses (BCoVs) are widespread around the world and cause enteric or respiratory infections among cattle. The current study includes 13 samples from BCoVs collected in Normandy during an 11-year period (from 2003 to 2014), 16 French HCoV-OC43s, and 113 BCoVs or BCoVs-like sequence data derived from partial or complete genome sequences available on GenBank. According to a genotyping method developed previously for HCoV-OC43, BCoVs and BCoVs-like are distributed on three main sub-clusters named C1, C2, and C3. Sub-cluster C1 includes BCoVs and BCoVs-like from America and Asia. Sub-cluster C2 includes BCoVs from Europe. Sub-cluster C3 includes prototype, vaccine, or attenuated BCoV strains. The phylogenetic analyses revealed the monophyletic status of the BCoVs from France reported here for the first time. Moreover, BCoV exhibits a relative genetic stability when compared to HCoV-OC43 we previously described from the same region. The numerous recombination detected between HCoV-OC43 were much less frequent for BCoV. The analysis points thus to the influence of different evolutive constraints in these two close groups., Graphical abstract Image 1, Highlight • We develop a genotyping methodology for BCoVs. • We report first BCoV partial genomic data from France. • We observe a different evolutive patterns for the BCoV and HCoV-OC43. • We don't report the existence of recombinant variants among BCoVs. • We show a geographical distribution of BCoVs.

Published
2016

20. Viral etiology of severe acute respiratory infections in hospitalized children in Cameroon, 2011-2013

Author

Suzie Moyo‐Tetang, Astrid Vabret, Mohamadou Njankouo-Ripa, Sebastien Kenmoe, Richard Njouom, Angeladine Kenne, Véronique Penlap Beng, Patrice Tchendjou, Marie-Astrid Vernet, Tatiana Mossus, Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), Université de Yaoundé I, Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Essos [Yaoundé, Cameroun], This work was funded by the International Network of Pasteur Institutes (PTR 351) and the 'Institut de Microbiologie et de Maladies Infectieuses (IMMI)' in France’., and We are grateful to all the nurses and other healthcare workers who collected specimens, data, and information and provided their support with clinical evaluations of patients during this study.

Subjects
MESH: Respiratory Tract Infections/epidemiology, MESH: Viruses/genetics, 0301 basic medicine, Male, Rhinovirus, Epidemiology, viruses, MESH: Viruses/classification, MESH: Hospitalization, medicine.disease_cause, 0302 clinical medicine, Cost of Illness, MESH: Child, MESH: Coinfection/virology, Human bocavirus, Nasopharynx, Medicine, MESH: Rhinovirus/isolation & purification, MESH: Carrier State/epidemiology, 030212 general & internal medicine, Cameroon, Prospective Studies, Child, Respiratory Tract Infections, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, MESH: Human bocavirus/genetics, MESH: Multiplex Polymerase Chain Reaction, Respiratory tract infections, biology, MESH: Viruses/isolation & purification, Coinfection, MESH: Respiratory Syncytial Virus, Human/genetics, virus diseases, MESH: Rhinovirus/genetics, MESH: Cost of Illness, MESH: Infant, 3. Good health, MESH: Acute Disease/epidemiology, Hospitalization, Human Parainfluenza Virus, Infectious Diseases, Child, Preschool, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Acute Disease, Carrier State, Epidemiological Monitoring, Viruses, MESH: Cameroon/epidemiology, Female, Original Article, Seasons, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Adolescent, etiology, 030106 microbiology, virus, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, 03 medical and health sciences, MESH: Carrier State/virology, Human metapneumovirus, Internal medicine, MESH: Nasopharynx/virology, MESH: Respiratory Syncytial Virus, Human/isolation & purification, Humans, MESH: Human bocavirus/isolation & purification, severe acute respiratory infections, MESH: Adolescent, MESH: Humans, business.industry, MESH: Child, Preschool, Public Health, Environmental and Occupational Health, Infant, Original Articles, medicine.disease, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Virology, MESH: Prospective Studies, MESH: Male, Respiratory Syncytial Virus, Human, Africa, Etiology, Enterovirus, MESH: Epidemiological Monitoring, business, MESH: Seasons, MESH: Female, Multiplex Polymerase Chain Reaction, MESH: Respiratory Tract Infections/virology
Abstract

International audience; BACKGROUND: Severe acute respiratory illness (SARI) is recognized as an important cause of morbidity, mortality, and hospitalization among children in developing countries. Little is known, however, in tropical countries like Cameroon about the cause and seasonality of respiratory infections, especially in hospitalized settings.OBJECTIVES: Our study investigates the viral etiology and seasonality of SARI in hospitalized children in Yaounde, Cameroon.METHODS: Prospective clinic surveillance was conducted to identify hospitalized children aged ≤15 years presenting with respiratory symptoms ≤5-day duration. Demographic and clinical data, and respiratory specimens were collected. Nasopharyngeal samples were tested for 17 respiratory viruses using a multiplex polymerase chain reaction. The viral distribution and demographic data were statistically analyzed.RESULTS: From September 2011 through September 2013, 347 children aged ≤15 years were enrolled. At least one virus was identified in each of 65·4% children, of which 29·5% were coinfections; 27·3% were positive for human adenovirus (hAdV), 13·2% for human respiratory syncytial virus (hRSV), 11·5% for rhinovirus/enterovirus (RV/EV), 10·6% for human bocavirus (hBoV), 9·8% for influenza virus (Inf), 6·6% for human parainfluenza virus (hPIV), 5·7% for human coronavirus (hCoV), and 2·3% for human metapneumovirus (hMPV). While hRSV showed seasonal patterns, hAdV and RV/EV were detected throughout the year and no evident temporal patterns were observed for the remaining viruses.CONCLUSION: Respiratory viruses were associated with a high burden of hospitalizations among children in Cameroon. Nevertheless, additional studies evaluating asymptomatic Cameroonian children will be important in understanding the relationship between viral carriage and disease.

Published
2016

21. A human coronavirus responsible for the common cold massively kills dendritic cells but not monocytes

Author

Matthew L. Albert, Frédéric Tangy, Astrid Vabret, Jean K. Millet, Valérie Lorin, Béatrice Nal, Pierre-Olivier Vidalain, Helen K. W. Law, Nicolas Escriou, Mariana Mesel-Lemoine, Génomique Virale et Vaccination, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre de recherche Université de Hong-Kong-Pasteur, Réseau International des Instituts Pasteur (RIIP), Department of Anatomy [HKU], The University of Hong Kong (HKU), Immunobiologie des Cellules Dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche Risques Microbiens (U2RM), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Réseau International des Instituts Pasteur ( RIIP ) -Centre de Recherche Université de Hong-Kong-Pasteur, The University of Hong Kong ( HKU ), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Unité de Recherche Risques Microbiens ( U2RM ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ), RAFFINAGE (RAFFINAGE), Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Département de pharmacochimie moléculaire [1999-2015] (DPM [1999-2015]), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Génétique Moléculaire des Virus Respiratoires, and Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Programmed cell death, Human coronavirus 229E, Fas Ligand Protein, Immunology, Common Cold, Antigens, CD34, Respiratory Mucosa, Biology, CD13 Antigens, Virus Replication, Dendritic cells, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Microbiology, [ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Giant Cells, Monocytes, TNF-Related Apoptosis-Inducing Ligand, 03 medical and health sciences, 0302 clinical medicine, Immune system, Antigen, Cytopathogenic Effect, Viral, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Coronavirus 229E, Human, Virology, Humans, 030304 developmental biology, 0303 health sciences, Syncytium, Cell Death, Tumor Necrosis Factor-alpha, virus diseases, Dendritic Cells, biology.organism_classification, 3. Good health, Virus-Cell Interactions, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Viral replication, Insect Science, Caspases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Respiratory epithelium, Tumor necrosis factor alpha, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology
Abstract

Human coronaviruses are associated with upper respiratory tract infections that occasionally spread to the lungs and other organs. Although airway epithelial cells represent an important target for infection, the respiratory epithelium is also composed of an elaborate network of dendritic cells (DCs) that are essential sentinels of the immune system, sensing pathogens and presenting foreign antigens to T lymphocytes. In this report, we show that in vitro infection by human coronavirus 229E (HCoV-229E) induces massive cytopathic effects in DCs, including the formation of large syncytia and cell death within only few hours. In contrast, monocytes are much more resistant to infection and cytopathic effects despite similar expression levels of CD13, the membrane receptor for HCoV-229E. While the differentiation of monocytes into DCs in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4 requires 5 days, only 24 h are sufficient for these cytokines to sensitize monocytes to cell death and cytopathic effects when infected by HCoV-229E. Cell death induced by HCoV-229E is independent of TRAIL, FasL, tumor necrosis factor alpha, and caspase activity, indicating that viral replication is directly responsible for the observed cytopathic effects. The consequence of DC death at the early stage of HCoV-229E infection may have an impact on the early control of viral dissemination and on the establishment of long-lasting immune memory, since people can be reinfected multiple times by HCoV-229E.

Published
2012

22. [Untitled]

Author

Kin, Nathalie, Guerard, Pauline, Diancourt, Laure, Caro, Valérie, Vabret, Astrid, Ar Gouilh, Meriadeg, Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Environnement et Risques infectieux - Environment and Infectious Risks (ERI), Institut Pasteur [Paris], Service de Virologie [CHU Caen], 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)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), and Institut Pasteur [Paris] (IP)

Subjects
0301 basic medicine, Whole genome sequencing, Strain (biology), Biology, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Virology, 03 medical and health sciences, 030104 developmental biology, Viruses, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Genetics, Molecular Biology, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Bovine coronavirus
Abstract

Accession number(s) : The complete genome sequence sequence of the BCoV/FRA-EPI/CAEN/2014/13 isolate has been deposited in GenBank under the accession number KX982264.; International audience; We sequenced the first Bovine coronavirus (BCoV) complete genome sequence from France. This BCoV was directly sequenced from a fecal sample collected from a calf in Normandy in 2014.

23. [Untitled]

Author

Nathalie Kin, Fabien Miszczak, Wei Lin, Meriadeg Ar Gouilh, Astrid Vabret, Epicorem Consortium, Unité de Recherche Risques Microbiens (U2RM), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Environnement et Risques infectieux - Environment and Infectious Risks (ERI), Institut Pasteur [Paris], Epicorem Consortium, and Institut Pasteur [Paris] (IP)

Subjects
Male, genotype, viruses, lcsh:QR1-502, coronavirus, Sequence Homology, phylogeny, medicine.disease_cause, Genome, lcsh:Microbiology, law.invention, Coronavirus OC43, Human, law, Genotype, Cluster Analysis, Human coronavirus OC43, Respiratory Tract Infections, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Coronavirus, Recombination, Genetic, Genetics, 0303 health sciences, biology, virus diseases, sequencing, Middle Aged, 3. Good health, Infectious Diseases, Child, Preschool, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Recombinant DNA, RNA, Viral, Female, France, Coronavirus Infections, HCoV-OC43, Molecular Sequence Data, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Article, Viral Proteins, 03 medical and health sciences, Phylogenetics, Virology, Genetic variation, medicine, Humans, Gene, Aged, 030304 developmental biology, 030306 microbiology, Genetic Variation, Sequence Analysis, DNA, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, recombination
Abstract

International audience; Human coronavirus OC43 (HCoV-OC43) is one of five currently circulating human coronaviruses responsible for respiratory infections. Like all coronaviruses, it is characterized by its genome's high plasticity. The objectives of the current study were to detect genetically distinct genotypes and eventually recombinant genotypes in samples collected in Lower Normandy between 2001 and 2013. To this end, we sequenced complete nsp12, S, and N genes of 15 molecular isolates of HCoV-OC43 from clinical samples and compared them to available data from the USA, Belgium, and Hong-Kong. A new cluster E was invariably detected from nsp12, S, and N data while the analysis of nsp12 and N genes revealed the existence of new F and G clusters respectively. The association of these different clusters of genes in our specimens led to the description of thirteen genetically distinct genotypes, among which eight recombinant viruses were discovered. Identification of these recombinant viruses, together with temporal analysis OPEN ACCESS Viruses 2015, 7 2359 and tMRCA estimation, provides important information for understanding the dynamics of the evolution of these epidemic coronaviruses.

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