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Ebola viral dynamics in nonhuman primates provides insights into virus immuno-pathogenesis and antiviral strategies

التفاصيل البيبلوغرافية
العنوان: Ebola viral dynamics in nonhuman primates provides insights into virus immuno-pathogenesis and antiviral strategies
المؤلفون: Madelain, Vincent, Baize, Sylvain, Jacquot, Frédéric, Reynard, Stéphanie, Fizet, Alexandra, Barron, Stephane, Solas, Caroline, Lacarelle, Bruno, Carbonnelle, Caroline, Mentré, France, Raoul, Hervé, de Lamballerie, Xavier, Guedj, Jérémie
المساهمون: 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), 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), Laboratoire P4 - Jean Mérieux, Centre Européen de Virologie/Immunologie-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Emergence des Pathologies Virales (EPV), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM), This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 666092, and from the St. Luke’s International University (Tokyo, Japan) in the framework of Research Program on Emerging and Re-emerging Infectious Diseases of the Japan Agency for Medical Research and Development (AMED)., European Project: 666092,H2020,H2020-Adhoc-2014-20,REACTION(2014), 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] (IP), Baize, Sylvain, Evaluation of the efficacy and of the antiviral activity of T-705 (favipiravir) duringEbola virus infection in non-human primates humans - REACTION - - H20202014-11-01 - 2016-10-31 - 666092 - VALID, 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 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]
المصدر: Nature Communications
Nature Communications, 2018, 9 (1), pp.4013. ⟨10.1038/s41467-018-06215-z⟩
Nature Communications, Vol 9, Iss 1, Pp 1-11 (2018)
Nature Communications, Nature Publishing Group, 2018, 9, ⟨10.1038/s41467-018-06215-z⟩
Nature Communications, Nature Publishing Group, 2018, 9 (1), pp.4013. ⟨10.1038/s41467-018-06215-z⟩
بيانات النشر: HAL CCSD, 2018.
سنة النشر: 2018
مصطلحات موضوعية: MESH: Antiviral Agents, Time Factors, [SDV]Life Sciences [q-bio], Science, viruses, Antiviral Agents, Article, Animals, MESH: Animals, MESH: Ebolavirus, lcsh:Science, MESH: Models, Theoretical, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Cytokines, MESH: Host-Pathogen Interactions, MESH: Macaca, MESH: Time Factors, Interferon-alpha, Hemorrhagic Fever, Ebola, Models, Theoretical, Viral Load, Ebolavirus, Amides, Survival Analysis, MESH: Amides, Disease Models, Animal, Pyrazines, MESH: Pyrazines, MESH: Survival Analysis, Host-Pathogen Interactions, MESH: Hemorrhagic Fever, Ebola, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Cytokines, Macaca, Female, lcsh:Q, MESH: Disease Models, Animal, MESH: Interferon-alpha, MESH: Viral Load, MESH: Female
الوصف: Despite several clinical trials implemented, no antiviral drug could demonstrate efficacy against Ebola virus. In non-human primates, early initiation of polymerase inhibitors favipiravir and remdesivir improves survival, but whether they could be effective in patients is unknown. Here we analyze the impact of antiviral therapy by using a mathematical model that integrates virological and immunological data of 44 cynomolgus macaques, left untreated or treated with favipiravir. We estimate that favipiravir has a ~50% efficacy in blocking viral production, which results in reducing virus growth and cytokine storm while IFNα reduces cell susceptibility to infection. Simulating the effect of delayed initiations of treatment, our model predicts survival rates of 60% for favipiravir and 100% for remdesivir when treatment is initiated within 3 and 4 days post infection, respectively. These results improve the understanding of Ebola immuno-pathogenesis and can help optimize antiviral evaluation in future outbreaks.
Optimization of antiviral therapy can be crucial in the management of Ebola virus outbreaks. Here, Madelain et al. use an integrative mathematical model to correlate the dose and the time of treatment initiation with survival rate, enhanced immune response and viral clearance.
وصف الملف: application/pdf
اللغة: English
تدمد: 2041-1723
URL الوصول: https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::d154ac0e471157d76dc4db477c6eb882
https://hal-pasteur.archives-ouvertes.fr/pasteur-03236192/document
حقوق: OPEN
رقم الأكسشن: edsair.pmid.dedup....d154ac0e471157d76dc4db477c6eb882
قاعدة البيانات: OpenAIRE
الوصف
تدمد:20411723