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16 results on '"Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)"'

1. Toward Tightly Tuned Gene Expression Following Lentiviral Vector Transduction

Author

Page, Audrey, Fusil, Floriane, François-Loïc, Cosset, Virus enveloppés, vecteurs et immunothérapie – Enveloped viruses, Vectors and Immuno-therapy (EVIR), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), 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), Référent HAL, CIRI, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
promoter, [SDV]Life Sciences [q-bio], Genetic Vectors, Lentivirus, transgene, Gene Transfer Techniques, lcsh:QR1-502, Gene Expression, lentiviral vectors, integration, Genetic Therapy, Review, Cellular Reprogramming, lcsh:Microbiology, [SDV] Life Sciences [q-bio], Gene Expression Regulation, Transduction, Genetic, sensor, Animals, Humans, Transgenes, synthetic biology, Promoter Regions, Genetic, induction, signal
Abstract

International audience; Lentiviral vectors are versatile tools for gene delivery purposes. While in the earlier versions of retroviral vectors, transgene expression was controlled by the long terminal repeats (LTRs), the latter generations of vectors, including those derived from lentiviruses, incorporate internal constitutive or regulated promoters in order to regulate transgene expression. This allows to temporally and/or quantitatively control transgene expression, which is required for many applications such as for clinical applications, when transgene expression is required in specific tissues and at a specific timing. Here we review the main systems that have been developed for transgene regulated expression following lentiviral gene transfer. First, the induction of gene expression can be triggered either by external or by internal cues. Indeed, these regulated vector systems may harbor promoters inducible by exogenous stimuli, such as small molecules (e.g., antibiotics) or temperature variations, offering the possibility to tune rapidly transgene expression in case of adverse events. Second, expression can be indirectly adjusted by playing on inserted sequence copies, for instance by gene excision. Finally, synthetic networks can be developed to sense specific endogenous signals and trigger defined responses after information processing. Regulatable lentiviral vectors (LV)-mediated transgene expression systems have been widely used in basic research to uncover gene functions or to temporally reprogram cells. Clinical applications are also under development to induce therapeutic molecule secretion or to implement safety switches. Such regulatable approaches are currently focusing much attention and will benefit from the development of other technologies in order to launch autonomously controlled systems.

Published
2020

2. In Vitro Combinations of Baloxavir Acid and Other Inhibitors against Seasonal Influenza A Viruses

Author

Andrés Pizzorno, Yacine Abed, Blandine Padey, Guy Boivin, Olivier Terrier, Liva Checkmahomed, Mariana Baz, Manuel Rosa-Calatrava, Université Laval [Québec] (ULaval), Signia Therapeutics SAS [Villeubane], Virpath-Grippe, de l'émergence au contrôle -- Virpath-Influenza, from emergence to control (Virpath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, 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), and Terrier, Olivier

Subjects
0301 basic medicine, lcsh:QR1-502, Drug resistance, Pharmacology, Virus Replication, Guanidines, lcsh:Microbiology, neuraminidase inhibitors, Madin Darby Canine Kidney Cells, chemistry.chemical_compound, 0302 clinical medicine, Influenza A Virus, H1N1 Subtype, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Zanamivir, 030212 general & internal medicine, media_common, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, baloxavir, biology, Triazines, Drug Synergism, A(H1N1) virus, 3. Good health, Drug Combinations, Infectious Diseases, Pyrazines, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, influenza, A(H3N2) virus, Drug, Dibenzothiepins, Oseltamivir, Pyridones, media_common.quotation_subject, Morpholines, Acids, Carbocyclic, Neuraminidase, Favipiravir, Antiviral Agents, Virus, Article, Cell Line, 03 medical and health sciences, Viral Proteins, Dogs, Orthomyxoviridae Infections, Virology, Drug Resistance, Viral, Ribavirin, Animals, Viability assay, Nucleic Acid Synthesis Inhibitors, combination, Influenza A Virus, H3N2 Subtype, Amides, 030104 developmental biology, chemistry, human airway epithelium, biology.protein, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, polymerase inhibitors
Abstract

International audience; Two antiviral classes, the neuraminidase inhibitors (NAIs) and polymerase inhibitors (baloxavir marboxil and favipiravir) can be used to prevent and treat influenza infections during seasonal epidemics and pandemics. However, prolonged treatment may lead to the emergence of drug resistance. Therapeutic combinations constitute an alternative to prevent resistance and reduce antiviral doses. Therefore, we evaluated in vitro combinations of baloxavir acid (BXA) and other approved drugs against influenza A(H1N1)pdm09 and A(H3N2) subtypes. The determination of an effective concentration inhibiting virus cytopathic effects by 50% (EC50) for each drug and combination indexes (CIs) were based on cell viability. CompuSyn software was used to determine synergism, additivity or antagonism between drugs. Combinations of BXA and NAIs or favipiravir had synergistic effects on cell viability against the two influenza A subtypes. Those effects were confirmed using a physiological and predictive ex vivo reconstructed human airway epithelium model. On the other hand, the combination of BXA and ribavirin showed mixed results. Overall, BXA stands as a good candidate for combination with several existing drugs, notably oseltamivir and favipiravir, to improve in vitro antiviral activity. These results should be considered for further animal and clinical evaluations.

Published
2020
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3. Autophagy Promotes Infectious Particle Production of Mopeia and Lassa Viruses

Author

Sylvain Baize, Sophie Krieger, Nicolas Baillet, Alexandra Journeaux, Valérie Caro, Pierre-Olivier Vidalain, Frédéric Tangy, Biologie des Infections Virales Émergentes - Biology of Emerging Viral Infections (UBIVE), 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)-Institut Pasteur [Paris], Environnement et Risques infectieux - Environment and Infectious Risks (ERI), Institut Pasteur [Paris], Génomique Virale et Vaccination, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), N.B. held a fellowship from the Délégation Générale de l’Armement (French Army). This work was supported by the Fondation pour l’Innovation en Infectiologie (FINOVI) (Lyon, France) and the Fondation pour la Recherche Médicale (FRM) (France) and an internal grant from the Institut Pasteur (PTR 414), MATEO, MATHIEU, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)

Subjects
0301 basic medicine, autophagy, replication, TAX1BP1, Cell, lcsh:QR1-502, MOPV, medicine.disease_cause, lcsh:Microbiology, Article, 03 medical and health sciences, LASV, Two-Hybrid System Techniques, Virology, Chlorocebus aethiops, medicine, NDP52, Z matrix protein, Animals, Humans, Lassa virus, Vero Cells, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Arenavirus, 030102 biochemistry & molecular biology, biology, High mortality, Autophagy, Intracellular Signaling Peptides and Proteins, Nuclear Proteins, biology.organism_classification, Pathogenicity, Cellular defense, 3. Good health, Neoplasm Proteins, 030104 developmental biology, medicine.anatomical_structure, HEK293 Cells, Infectious Diseases, yeast two-hybrid screening, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Mammarenavirus, HeLa Cells
Abstract

International audience; Lassa virus (LASV) and Mopeia virus (MOPV) are two closely related Old-World mammarenaviruses. LASV causes severe hemorrhagic fever with high mortality in humans, whereas no case of MOPV infection has been reported. Comparing MOPV and LASV is a powerful strategy to unravel pathogenic mechanisms that occur during the course of pathogenic arenavirus infection. We used a yeast two-hybrid approach to identify cell partners of MOPV and LASV Z matrix protein in which two autophagy adaptors were identified, NDP52 and TAX1BP1. Autophagy has emerged as an important cellular defense mechanism against viral infections but its role during arenavirus infection has not been shown. Here, we demonstrate that autophagy is transiently induced by MOPV, but not LASV, in infected cells two days after infection. Impairment of the early steps of autophagy significantly decreased the production of MOPV and LASV infectious particles, whereas a blockade of the degradative steps impaired only MOPV infectious particle production. Our study provides insights into the role played by autophagy during MOPV and LASV infection and suggests that this process could partially explain their different pathogenicity.

Published
2019
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4. Overview of HCV Life Cycle with a Special Focus on Current and Possible Future Antiviral Targets

Author

Bertrand Boson, François-Loïc Cosset, Nathalie Alazard-Dany, Solène Denolly, 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), Virus enveloppés, vecteurs et immunothérapie – Enveloped viruses, Vectors and Immuno-therapy (EVIR), 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), 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), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL)

Subjects
0301 basic medicine, medicine.medical_specialty, lcsh:QR1-502, Review, Hepacivirus, DIRECT ACTING ANTIVIRALS, Antiviral Agents, lcsh:Microbiology, 03 medical and health sciences, Global population, 0302 clinical medicine, Virology, Medicine, Humans, Protease Inhibitors, Molecular Targeted Therapy, Intensive care medicine, DAA, Focus (computing), business.industry, Hepatitis C, medicine.disease, 3. Good health, 030104 developmental biology, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HCV, 030211 gastroenterology & hepatology, business, antiviral targets
Abstract

International audience; Hepatitis C infection is the leading cause of liver diseases worldwide and a major health concern that affects an estimated 3% of the global population. Novel therapies available since 2014 and 2017 are very efficient and the WHO considers HCV eradication possible by the year 2030. These treatments are based on the so-called direct acting antivirals (DAAs) that have been developed through research efforts by academia and industry since the 1990s. After a brief overview of the HCV life cycle, we describe here the functions of the different targets of current DAAs, the mode of action of these DAAs and potential future inhibitors.

Published
2019

5. Detection and Characterization of Homologues of Human Hepatitis Viruses and Pegiviruses in Rodents and Bats in Vietnam

Author

Van Nguyen, D, Van Nguyen, C, Bonsall, D, Ngo, T, Carrique-Mas, J, Pham, A, Bryant, J, Thwaites, G, Baker, S, Woolhouse, M, Simmonds, P, Nuffield Department of Clinical Medicine [Oxford], University of Oxford, Oxford University Clinical Research Unit [Ho Chi Minh City] (OUCRU), Centre for Tropical Medicine and Global Health [Oxford, UK], Nuffield Department of Medicine [Oxford, UK] (Big Data Institute), University of Oxford-University of Oxford, Laboratoire des pathogènes émergents -- Emerging Pathogens Laboratory (LPE-Fondation Mérieux), 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), Centre for Immunity, Infection and Evolution, University of Edinburgh, Van Nguyen, Dung [0000-0001-9390-9990], Apollo - University of Cambridge Repository, University of Oxford [Oxford], University of Oxford [Oxford]-University of Oxford [Oxford], 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), and Wellcome Trust

Subjects
0301 basic medicine, Rodent, Hepacivirus, lcsh:QR1-502, Genome, lcsh:Microbiology, Hepatitis, Chiroptera, Zoonoses, Rhizomys, homologues, Public Health Surveillance, Viral, Phylogeny, biology, Transmission (medicine), 3. Good health, Infectious Diseases, Vietnam, Hepatitis, Viral, Animal, rodents, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, bats, pegiviruses, hepatitis viruses, [SDV.IMM]Life Sciences [q-bio]/Immunology, RNA, Viral, 0605 Microbiology, Human, Hepatitis, Viral, Human, Pegivirus, Rodentia, Genome, Viral, Article, 03 medical and health sciences, Phylogenetics, Virology, biology.animal, Journal Article, Animals, Humans, Animal, Bamboo rat, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 030104 developmental biology, RNA
Abstract

International audience; Rodents and bats are now widely recognised as important sources of zoonotic virus infections in other mammals, including humans. Numerous surveys have expanded our knowledge of diverse viruses in a range of rodent and bat species, including their origins, evolution, and range of hosts. In this study of pegivirus and human hepatitis-related viruses, liver and serum samples from Vietnamese rodents and bats were examined by PCR and sequencing. Nucleic acids homologous to human hepatitis B, C, E viruses were detected in liver samples of 2 (1.3%) of 157 bats, 38 (8.1%), and 14 (3%) of 470 rodents, respectively. Hepacivirus-like viruses were frequently detected (42.7%) in the bamboo rat, Rhizomys pruinosus, while pegivirus RNA was only evident in 2 (0.3%) of 638 rodent serum samples. Complete or near-complete genome sequences of HBV, HEV and pegivirus homologues closely resembled those previously reported from rodents and bats. However, complete coding region sequences of the rodent hepacivirus-like viruses substantially diverged from all of the currently classified variants and potentially represent a new species in the Hepacivirus genus. Of the viruses identified, their routes of transmission and potential to establish zoonoses remain to be determined.

Published
2018

6. HTLV-1, the Other Pathogenic Yet Neglected Human Retrovirus: From Transmission to Therapeutic Treatment

Author

Futsch, Nicolas, Mahieux, Renaud, Dutartre, Hélène, Equipe labellisée Ligue contre le Cancer, Oncogenèse rétrovirale – Retroviral Oncogenesis (OR), 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), Davoine, Laure-Hélène, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
CD4-Positive T-Lymphocytes, [SDV.IMM] Life Sciences [q-bio]/Immunology, viruses, lcsh:QR1-502, HIV Infections, Review, Virus Replication, ATLL, lcsh:Microbiology, TSP/HAM, Drug Discovery, Humans, Leukemia-Lymphoma, Adult T-Cell, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Human T-lymphotropic virus 1, Coinfection, viral transmission, virus diseases, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, HTLV-I Infections, Paraparesis, Tropical Spastic, HTLV-1, treatments, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract

International audience; Going back to their discovery in the early 1980s, both the Human T-cell Leukemia virus type-1 (HTLV-1) and the Human Immunodeficiency Virus type-1 (HIV-1) greatly fascinated the virology scene, not only because they were the first human retroviruses discovered, but also because they were associated with fatal diseases in the human population. In almost four decades of scientific research, both viruses have had different fates, HTLV-1 being often upstaged by HIV-1. However, although being very close in terms of genome organization, cellular tropism, and viral replication, HIV-1 and HTLV-1 are not completely commutable in terms of treatment, especially because of the opposite fate of the cells they infect: death versus immortalization, respectively. Nowadays, the antiretroviral therapies developed to treat HIV-1 infected individuals and to limit HIV-1 spread among the human population have a poor or no effect on HTLV-1 infected individuals, and thus, do not prevent the development of HTLV-1-associated diseases, which still lack highly efficient treatments. The present review mainly focuses on the course of HTLV-1 infection, from the initial infection of the host to diseases development and associated treatments, but also investigates HIV-1/HTLV-1 co-infection events and their impact on diseases development.

Published
2017

7. Autophagy in Measles Virus Infection

Author

Rozières, Aurore, Viret, Christophe, Faure, Mathias, Autophagie infection et immunité - Autophagy Infection Immunity (APY), 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 International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
T6BP, autophagy, lcsh:QR1-502, Cell Cycle Proteins, Review, Virus Replication, lcsh:Microbiology, Membrane Cofactor Protein, OPTN, GTP-Binding Proteins, Transcription Factor TFIIIA, Sequestosome-1 Protein, NDP52, Humans, CD46, autophagy receptors, selective autophagy, Intracellular Signaling Peptides and Proteins, Membrane Transport Proteins, Nuclear Proteins, IRGM, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Neoplasm Proteins, Measles virus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Measles
Abstract

International audience; Autophagy is a biological process that helps cells to recycle obsolete cellular components and which greatly contributes to maintaining cellular integrity in response to environmental stress factors. Autophagy is also among the first lines of cellular defense against invading microorganisms, including viruses. The autophagic destruction of invading pathogens, a process referred to as xenophagy, involves cytosolic autophagy receptors, such as p62/SQSTM1 (Sequestosome 1) or NDP52/CALCOCO2 (Nuclear Dot 52 KDa Protein/Calcium Binding And Coiled-Coil Domain 2), which bind to microbial components and target them towards growing autophagosomes for degradation. However, most, if not all, infectious viruses have evolved molecular tricks to escape from xenophagy. Many viruses even use autophagy, part of the autophagy pathway or some autophagy-associated proteins, to improve their infectious potential. In this regard, the measles virus, responsible for epidemic measles, has a unique interface with autophagy as the virus can induce multiple rounds of autophagy in the course of infection. These successive waves of autophagy result from distinct molecular pathways and seem associated with anti- and/or pro-measles virus consequences. In this review, we describe what the autophagy-measles virus interplay has taught us about both the biology of the virus and the mechanistic orchestration of autophagy.

Published
2017

8. Distinct Contributions of Autophagy Receptors in Measles Virus Replication

Author

Mathias Faure, Renaud Mahieux, Carole Kretz-Remy, Mathieu Claviere, Pauline Verlhac, Christophe Viret, Aurore Rozières, Denitsa S Petkova, Joël Baguet, Autophagie infection et immunité - Autophagy Infection Immunity (APY), 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), Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Oncogenèse rétrovirale – Retroviral Oncogenesis (OR), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Autophagosome, autophagosome, Cell Cycle Proteins, Virus Replication, Virus, Article, Measles virus, autophagy receptor, 03 medical and health sciences, Viral Proteins, Virology, Phagosomes, Transcription Factor TFIIIA, Autophagy, Humans, Receptor, Optineurin, 030102 biochemistry & molecular biology, biology, maturation, Intracellular parasite, Intracellular Signaling Peptides and Proteins, Membrane Transport Proteins, Nuclear Proteins, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Cell biology, Neoplasm Proteins, 030104 developmental biology, Infectious Diseases, Viral replication, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Host-Pathogen Interactions, measles virus, [SDV.IMM]Life Sciences [q-bio]/Immunology, Carrier Proteins, Lysosomes, HeLa Cells, Measles
Abstract

International audience; Autophagy is a potent cell autonomous defense mechanism that engages the lysosomal pathway to fight intracellular pathogens. Several autophagy receptors can recognize invading pathogens in order to target them towards autophagy for their degradation after the fusion of pathogen-containing autophagosomes with lysosomes. However, numerous intracellular pathogens can avoid or exploit autophagy, among which is measles virus (MeV). This virus induces a complete autophagy flux, which is required to improve viral replication. We therefore asked how measles virus interferes with autophagy receptors during the course of infection. We report that in addition to NDP52/CALCOCO_2 and OPTINEURIN/OPTN, another autophagy receptor, namely T6BP/TAXIBP1, also regulates the maturation of autophagosomes by promoting their fusion with lysosomes, independently of any infection. Surprisingly, only two of these receptors, NDP52 and T6BP, impacted measles virus replication, although independently, and possibly through physical interaction with MeV proteins. Thus, our results suggest that a restricted set of autophagosomes is selectively exploited by measles virus to replicate in the course of infection.

Published
2017

9. Involvement of Surfactant Protein D in Ebola Virus Infection Enhancement via Glycoprotein Interaction

Author

Favier, Anne-Laure, Reynard, Olivier, Gout, Evelyne, van Eijk, Martin, Haagsman, Henk P, Crouch, Erika, Volchkov, Viktor, Peyrefitte, Christophe, Thielens, Nicole M, LS Moleculaire Afweer, dI&I I&I-3, Dep Infectieziekten Immunologie, Institut de Recherche Biomédicale des Armées (IRBA), Bases moléculaires de la pathogénicité virale – Molecular Basis of Viral Pathogenicity (BMPV), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), 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), Division of Molecular Host Defence, Department of Infectious Diseases and Immunology, Department of Pathology and Immunology (DEPARTMENT OF PATHOLOGY AND IMMUNOLOGY), Washington University in Saint Louis (WUSTL), Unité de Virologie, Institut de Recherches Biomédicales des Armées, SPR platform, Cell Imaging platform, LS Moleculaire Afweer, dI&I I&I-3, Dep Infectieziekten Immunologie, Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), 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), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)

Subjects
glycoprotein, pig, 0301 basic medicine, Swine, viruses, lcsh:QR1-502, medicine.disease_cause, lcsh:Microbiology, collectin, Ebola virus, Chlorocebus aethiops, innate immunity, Innate immunity, chemistry.chemical_classification, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], SP-D, virus diseases, Ebolavirus, Pulmonary Surfactant-Associated Protein D, 3. Good health, Infectious Diseases, Reston virus, surfactant protein, Protein Binding, Interaction, interaction, Collectin, Biology, Article, Virus, Viral Proteins, 03 medical and health sciences, Virology, medicine, Animals, Humans, Vero Cells, Glycoproteins, Pig, Innate immune system, Host Microbial Interactions, Outbreak, Lectin, Surfactant protein D, Biomolecules (q-bio.BM), Hemorrhagic Fever, Ebola, Collectins, Immunity, Innate, HEK293 Cells, 030104 developmental biology, Quantitative Biology - Biomolecules, chemistry, FOS: Biological sciences, biology.protein, Glycoprotein
Abstract

International audience; Since the largest 2014⁻2016 Ebola virus disease outbreak in West Africa, understanding of Ebola virus infection has improved, notably the involvement of innate immune mediators. Amongst them, collectins are important players in the antiviral innate immune defense. A screening of Ebola glycoprotein (GP)-collectins interactions revealed the specific interaction of human surfactant protein D (hSP-D), a lectin expressed in lung and liver, two compartments where Ebola was found in vivo. Further analyses have demonstrated an involvement of hSP-D in the enhancement of virus infection in several in vitro models. Similar effects were observed for porcine SP-D (pSP-D). In addition, both hSP-D and pSP-D interacted with Reston virus (RESTV) GP and enhanced pseudoviral infection in pulmonary cells. Thus, our study reveals a novel partner of Ebola GP that may participate to enhance viral spread.

Published
2018

10. Immune Responses and Lassa Virus Infection

Author

Delphine Pannetier, Sylvain Baize, Marion Russier, Biologie des Infections Virales Émergentes - Biology of Emerging Viral Infections (UBIVE), 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)-Institut Pasteur [Paris] (IP), 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), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]

Subjects
MESH: Killer Cells, Natural, [SDV]Life Sciences [q-bio], viruses, T-Lymphocytes, lcsh:QR1-502, Antigen-Presenting Cells, Disease, Review, MESH: Lassa Fever, medicine.disease_cause, lcsh:Microbiology, Pathogenesis, 03 medical and health sciences, Immune system, Lassa Fever, Immunity, Virology, medicine, Animals, Humans, MESH: Animals, MESH: Immunity, Humoral, Lassa fever, Lassa virus, 030304 developmental biology, 0303 health sciences, Arenavirus, MESH: Humans, biology, 030306 microbiology, MESH: Antigen-Presenting Cells, MESH: Lassa virus, virus diseases, medicine.disease, biology.organism_classification, immunity, 3. Good health, Immunity, Humoral, Killer Cells, Natural, Infectious Diseases, MESH: T-Lymphocytes, Viral replication, Immunology, T-cell responses, hemorrhagic fever
Abstract

International audience; Lassa fever is a hemorrhagic fever endemic to West Africa and caused by Lassa virus, an Old World arenavirus. It may be fatal, but most patients recover from acute disease and some experience asymptomatic infection. The immune mechanisms associated with these different outcomes have not yet been fully elucidated, but considerable progress has recently been made, through the use of in vitro human models and nonhuman primates, the only relevant animal model that mimics the pathophysiology and immune responses induced in patients. We discuss here the roles of the various components of the innate and adaptive immune systems in Lassa virus infection and in the control of viral replication and pathogenesis.

Published
2012

11. The Inside Out of Lentiviral Vectors

Author

Stéphanie Durand, Andrea Cimarelli, Ecole normale supérieure de Lyon (Ens Lyon), Equipe virus AAV et vecteurs AAV (INSERM U758/ ENS de Lyon), Institut National de la Santé et de la Recherche Médicale (INSERM), BioSciences Lyon-Gerland (BLG), École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Interaction hôte pathogène lors de l'infection lentivirale – Host-Pathogen Interaction during Lentiviral Infection (LP2L), 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), CIMARELLI, Andrea, École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)

Subjects
Genetic enhancement, Genetic Vectors, lcsh:QR1-502, Human immunodeficiency virus (HIV), Gene transfer, Review, Computational biology, Biology, medicine.disease_cause, lcsh:Microbiology, Genetic therapy, Viral vector, EIAV, 03 medical and health sciences, lentivirus, Virology, medicine, Animals, Humans, Myeloid Cells, Animal species, 030304 developmental biology, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Genetics, 0303 health sciences, lentiviral vector, 030302 biochemistry & molecular biology, Gene Transfer Techniques, HIV, Genetic Therapy, biology.organism_classification, gene therapy, FIV, Infectious Diseases, SIV, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Myeloid cells, Lentivirus
Abstract

International audience; Lentiviruses induce a wide variety of pathologies in different animal species. A common feature of the replicative cycle of these viruses is their ability to target non-dividing cells, a property that constitutes an extremely attractive asset in gene therapy. In this review, we shall describe the main basic aspects of the virology of lentiviruses that were exploited to obtain efficient gene transfer vectors. In addition, we shall discuss some of the hurdles that oppose the efficient genetic modification mediated by lentiviral vectors and the strategies that are being developed to circumvent them.

Published
2011

12. IFITMs from Naturally Infected Animal Species Exhibit Distinct Restriction Capacities against Toscana and Rift Valley Fever Viruses

Author

Marie-Pierre Confort, Maëva Duboeuf, Adrien Thiesson, Léa Pons, Federico Marziali, Sophie Desloire, Maxime Ratinier, Andrea Cimarelli, Frédérick Arnaud, Infections Virales et Pathologie Comparée - UMR 754 (IVPC), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Toscana virus, viral restriction, Infectious Diseases, Virology, [SDV]Life Sciences [q-bio], [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Rift Valley fever virus, IFITM
Abstract

International audience; Rift Valley Fever virus (RVFV) and Toscana virus (TOSV) are two pathogenic arthropod-borne viruses responsible for zoonotic infections in both humans and animals; as such, they represent a growing threat to public and veterinary health. Interferon-induced transmembrane (IFITM) proteins are broad inhibitors of a large panel of viruses belonging to various families and genera. However, little is known on the interplay between RVFV, TOSV, and the IFITM proteins derived from their naturally infected host species. In this study, we investigated the ability of human, bovine, and camel IFITMs to restrict RVFV and TOSV infection. Our results indicated that TOSV was extremely sensitive to inhibition by all the animal IFITMs tested, while RVFV was inhibited by human IFITM-2 and IFITM-3, but not IFITM-1, and exhibited a more heterogeneous resistance phenotype towards the individual bovine and camel IFITMs tested. Overall, our findings shed some light on the complex and differential interplay between two zoonotic viruses and IFITMs from their naturally infected animal species.

Published
2023
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13. Identification of a New Ribonucleoside Inhibitor of Ebola Virus Replication

Author

Xuan-Nhi Nguyen, Olivier Reynard, Andrea Cimarelli, Viktor E. Volchkov, Nathalie Alazard-Dany, Véronique Barateau, Bases moléculaires de la pathogénicité virale – Molecular Basis of Viral Pathogenicity (BMPV), 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), Interaction hôte pathogène lors de l'infection lentivirale – Host-Pathogen Interaction during Lentiviral Infection (LP2L), Bases moléculaires de la pathogénicité virale – Molecular Basis of Viral Pathogenicity, 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), Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Virologie humaine, École normale supérieure - Lyon (ENS Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Interaction hôte pathogène lors de l'infection lentivirale – Host-Pathogen Interaction during Lentiviral Infection, Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL)

Subjects
lcsh:QR1-502, Cytidine, medicine.disease_cause, Virus Replication, Antiviral Agents, lcsh:Microbiology, Cercopithecus aethiops, Marburg, 03 medical and health sciences, chemistry.chemical_compound, Virology, inhibitors, Chlorocebus aethiops, medicine, Animals, Vero Cells, ComputingMilieux_MISCELLANEOUS, Polymerase, 030304 developmental biology, Ebolavirus, 0303 health sciences, Ebola virus, biology, 030306 microbiology, Brief Report, Correction, Ribonucleoside, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, antiviral, Filovirus, 3. Good health, polymerase, Infectious Diseases, chemistry, Viral replication, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Ebola, biology.protein, Vero cell, [SDV.IMM]Life Sciences [q-bio]/Immunology, Nucleoside
Abstract

International audience; The current outbreak of Ebola virus (EBOV) in West Africa has claimed the lives of more than 15,000 people and highlights an urgent need for therapeutics capable of preventing virus replication. In this study we screened known nucleoside analogues for their ability to interfere with EBOV replication. Among them, the cytidine analogue β-d-N4-hydroxycytidine (NHC) demonstrated potent inhibitory activities against EBOV replication and spread at non-cytotoxic concentrations. Thus, NHC constitutes an interesting candidate for the development of a suitable drug treatment against EBOV.

Published
2015

14. The Relationship between DUGBE Virus Infection and Autophagy in Epithelial Cells

Author

Marie Moroso, Aurore Rozières, Pauline Verlhac, Florence Komurian-Pradel, Olivier Ferraris, Christophe N. Peyrefitte, Glaucia Paranhos-Baccalà, Christophe Viret, Mathias Faure, 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), Fondation Mérieux, and Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA)

Subjects
Nairobi sheep disease virus, [SDV]Life Sciences [q-bio], Proteins, epithelial cells, Dugbe orthonairovirus, Crimean–Congo hemorrhagic fever orthonairovirus, autophagy, MAP1LC3 lipidation, viral infection, Infectious Diseases, Virology, Sequestosome-1 Protein, Hemorrhagic Fever Virus, Crimean-Congo, Autophagy, Hepatocytes, Humans, Hemorrhagic Fever, Crimean
Abstract

International audience; Dugbe orthonairovirus (DUGV) is a tick-borne arbovirus within the order Bunyavirales. Although displaying mild pathogenic potential, DUGV is genetically related to the Crimean–Congo hemorrhagic fever virus (CCHFV), another orthonairovirus that causes severe liver dysfunction and hemorrhagic fever with a high mortality rate in humans. As we previously observed that CCHFV infection could massively recruit and lipidate MAP1LC3 (LC3), a core factor involved in the autophagic degradation of cytosolic components, we asked whether DUGV infection also substantially impacts the autophagy machinery in epithelial cells. We observed that DUGV infection does impose LC3 lipidation in cultured hepatocytes. DUGV infection also caused an upregulation of the MAP1LC3 and SQSTM1/p62 transcript levels, which were, however, more moderate than those seen during CCHFV infection. In contrast, unlike during CCHFV infection, the modulation of core autophagy factors could influence both LC3 lipidation and viral particle production: the silencing of ATG5 and/or ATG7 diminished the induction of LC3 lipidation and slightly upregulated the level of infectious DUGV particle production. Overall, the results are compatible with the notion that in epithelial cells infected with DUGV in vitro, the autophagy machinery may be recruited to exert a certain level of restriction on viral replication. Thus, the relationship between DUGV infection and autophagy in epithelial cells appears to present both similarities and distinctions with that seen during CCHFV infection.

Published
2022

15. Metagenomic Analysis Reveals High Abundance of Torque Teno Mini Virus in the Respiratory Tract of Children with Acute Respiratory Illness

Author

Antonin Bal, Gregory Destras, Marina Sabatier, Maxime Pichon, Hadrien Regue, Guy Oriol, Yves Gillet, Bruno Lina, Karen Brengel-Pesce, Laurence Josset, Florence Morfin, Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL), 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), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Pharmacologie des anti-infectieux et antibiorésistance (PHAR2), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, Unité Mixte bioMérieux-HCL, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Chauzy, Alexia, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Torque teno virus, metagenomics, torque teno virus, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Respiratory System, torque teno mini virus, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Anelloviridae, DNA Virus Infections, respiratory virus, Infectious Diseases, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, Respiratory Syncytial Virus, Human, acute respiratory infection, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Influenza, Human, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Humans, Child, Respiratory Tract Infections
Abstract

International audience; Human Anelloviridae is a highly prevalent viral family, including three main genera—Alphatorquevirus (Torque teno virus, TTV), Betatorquevirus (Torque teno mini virus, TTMV), and Gammatorquevirus (Torque teno midi virus, TTMDV). To date, the characterization of Anelloviridae in the respiratory tract of children with acute respiratory infection (ARI) has been poorly reported and mainly focused on TTV. We performed a metagenomic analysis of eight respiratory samples collected from children with an ARI of unknown etiology (eight samples tested negative with a multiplex PCR assay, out of the 39 samples initially selected based on negative routine diagnostic testing). A total of 19 pediatric respiratory samples that tested positive for respiratory syncytial virus (RSV, n = 13) or influenza virus (n = 6) were also sequenced. Anelloviridae reads were detected in 16/27 samples, including 6/8 negative samples, 7/13 RSV samples and 3/6 influenza samples. For samples with a detection of at least one Anelloviridae genus, TTMV represented 87.1 (66.1–99.2)% of Anelloviridae reads, while TTV and TTMDV represented 0.8 (0.0–9.6)% and 0.7 (0.0–7.1)%, respectively (p < 0.001). Our findings highlight a high prevalence of TTMV in respiratory samples of children with an ARI of unknown etiology, as well as in samples with an RSV or influenza infection. Larger studies are needed to explore the role of TTMV in childhood respiratory diseases.

Published
2022

16. Viral and Bacterial Co-Infections in the Lungs: Dangerous Liaisons

Author

Justine Oliva, Olivier Terrier, 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), Terrier, Olivier, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
respiratory syncytial virus, viruses, Pneumonia, Viral, Context (language use), Review, medicine.disease_cause, Microbiology, influenza virus, respiratory infections, 03 medical and health sciences, Antibiotic resistance, respiratory viruses, Virology, Pneumonia, Bacterial, medicine, Humans, Microbiome, Respiratory system, 030304 developmental biology, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, Respiratory tract infections, SARS-CoV-2, Coinfection, co-infections, superinfections, 030306 microbiology, business.industry, Microbiota, Disease Management, medicine.disease, Immunity, Innate, QR1-502, 3. Good health, Infectious Diseases, medicine.anatomical_structure, Superinfection, Host-Pathogen Interactions, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Immunology, Disease Susceptibility, business, Respiratory tract
Abstract

International audience; Respiratory tract infections constitute a significant public health problem, with a therapeutic arsenal that remains relatively limited and that is threatened by the emergence of antiviral and/or antibiotic resistance. Viral–bacterial co-infections are very often associated with the severity of these respiratory infections and have been explored mainly in the context of bacterial superinfections following primary influenza infection. This review summarizes our current knowledge of the mechanisms underlying these co-infections between respiratory viruses (influenza viruses, RSV, and SARS-CoV-2) and bacteria, at both the physiological and immunological levels. This review also explores the importance of the microbiome and the pathological context in the evolution of these respiratory tract co-infections and presents the different in vitro and in vivo experimental models available. A better understanding of the complex functional interactions between viruses/bacteria and host cells will allow the development of new, specific, and more effective diagnostic and therapeutic approaches.

Published
2021

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