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Quantification of Ebola virus replication kinetics in vitro

Mathematical modelling has successfully been used to provide quantitative descriptions of many viral infections, but for the Ebola virus, which requires biosafety level 4 facilities for experimentation, modelling can play a crucial role. Ebola virus modelling efforts have primarily focused on in viv...

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Autores principales: Liao, Laura E., Carruthers, Jonathan, Smither, Sophie J., Weller, Simon A., Williamson, Diane, Laws, Thomas R., García-Dorival, Isabel, Hiscox, Julian, Holder, Benjamin P., Beauchemin, Catherine A. A., Perelson, Alan S., López-García, Martín, Lythe, Grant, Barr, John N., Molina-París, Carmen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660928/
https://www.ncbi.nlm.nih.gov/pubmed/33137116
http://dx.doi.org/10.1371/journal.pcbi.1008375
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author Liao, Laura E.
Carruthers, Jonathan
Smither, Sophie J.
Weller, Simon A.
Williamson, Diane
Laws, Thomas R.
García-Dorival, Isabel
Hiscox, Julian
Holder, Benjamin P.
Beauchemin, Catherine A. A.
Perelson, Alan S.
López-García, Martín
Lythe, Grant
Barr, John N.
Molina-París, Carmen
author_facet Liao, Laura E.
Carruthers, Jonathan
Smither, Sophie J.
Weller, Simon A.
Williamson, Diane
Laws, Thomas R.
García-Dorival, Isabel
Hiscox, Julian
Holder, Benjamin P.
Beauchemin, Catherine A. A.
Perelson, Alan S.
López-García, Martín
Lythe, Grant
Barr, John N.
Molina-París, Carmen
author_sort Liao, Laura E.
collection PubMed
description Mathematical modelling has successfully been used to provide quantitative descriptions of many viral infections, but for the Ebola virus, which requires biosafety level 4 facilities for experimentation, modelling can play a crucial role. Ebola virus modelling efforts have primarily focused on in vivo virus kinetics, e.g., in animal models, to aid the development of antivirals and vaccines. But, thus far, these studies have not yielded a detailed specification of the infection cycle, which could provide a foundational description of the virus kinetics and thus a deeper understanding of their clinical manifestation. Here, we obtain a diverse experimental data set of the Ebola virus infection in vitro, and then make use of Bayesian inference methods to fully identify parameters in a mathematical model of the infection. Our results provide insights into the distribution of time an infected cell spends in the eclipse phase (the period between infection and the start of virus production), as well as the rate at which infectious virions lose infectivity. We suggest how these results can be used in future models to describe co-infection with defective interfering particles, which are an emerging alternative therapeutic.
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spelling pubmed-76609282020-11-18 Quantification of Ebola virus replication kinetics in vitro Liao, Laura E. Carruthers, Jonathan Smither, Sophie J. Weller, Simon A. Williamson, Diane Laws, Thomas R. García-Dorival, Isabel Hiscox, Julian Holder, Benjamin P. Beauchemin, Catherine A. A. Perelson, Alan S. López-García, Martín Lythe, Grant Barr, John N. Molina-París, Carmen PLoS Comput Biol Research Article Mathematical modelling has successfully been used to provide quantitative descriptions of many viral infections, but for the Ebola virus, which requires biosafety level 4 facilities for experimentation, modelling can play a crucial role. Ebola virus modelling efforts have primarily focused on in vivo virus kinetics, e.g., in animal models, to aid the development of antivirals and vaccines. But, thus far, these studies have not yielded a detailed specification of the infection cycle, which could provide a foundational description of the virus kinetics and thus a deeper understanding of their clinical manifestation. Here, we obtain a diverse experimental data set of the Ebola virus infection in vitro, and then make use of Bayesian inference methods to fully identify parameters in a mathematical model of the infection. Our results provide insights into the distribution of time an infected cell spends in the eclipse phase (the period between infection and the start of virus production), as well as the rate at which infectious virions lose infectivity. We suggest how these results can be used in future models to describe co-infection with defective interfering particles, which are an emerging alternative therapeutic. Public Library of Science 2020-11-02 /pmc/articles/PMC7660928/ /pubmed/33137116 http://dx.doi.org/10.1371/journal.pcbi.1008375 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
spellingShingle Research Article
Liao, Laura E.
Carruthers, Jonathan
Smither, Sophie J.
Weller, Simon A.
Williamson, Diane
Laws, Thomas R.
García-Dorival, Isabel
Hiscox, Julian
Holder, Benjamin P.
Beauchemin, Catherine A. A.
Perelson, Alan S.
López-García, Martín
Lythe, Grant
Barr, John N.
Molina-París, Carmen
Quantification of Ebola virus replication kinetics in vitro
title Quantification of Ebola virus replication kinetics in vitro
title_full Quantification of Ebola virus replication kinetics in vitro
title_fullStr Quantification of Ebola virus replication kinetics in vitro
title_full_unstemmed Quantification of Ebola virus replication kinetics in vitro
title_short Quantification of Ebola virus replication kinetics in vitro
title_sort quantification of ebola virus replication kinetics in vitro
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660928/
https://www.ncbi.nlm.nih.gov/pubmed/33137116
http://dx.doi.org/10.1371/journal.pcbi.1008375
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