Quantification of Ebola virus replication kinetics in vitro

Fuente: arXiv
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Hauptverfasser: Liao, Laura E., Carruthers, Jonathan, Smither, Sophie J., Team, CL4 Virology, Weller, Simon A., Williamson, Diane, Laws, Thomas R., Garcia-Dorival, Isabel, Hiscox, Julian, Holder, Benjamin P., Beauchemin, Catherine A. A., Perelson, Alan S., Lopez-Garcia, Martin, Lythe, Grant, Barr, John, Molina-Paris, Carmen
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Veröffentlicht: 2020
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author Liao, Laura E.
Carruthers, Jonathan
Smither, Sophie J.
Team, CL4 Virology
Weller, Simon A.
Williamson, Diane
Laws, Thomas R.
Garcia-Dorival, Isabel
Hiscox, Julian
Holder, Benjamin P.
Beauchemin, Catherine A. A.
Perelson, Alan S.
Lopez-Garcia, Martin
Lythe, Grant
Barr, John
Molina-Paris, Carmen
author_facet Liao, Laura E.
Carruthers, Jonathan
Smither, Sophie J.
Team, CL4 Virology
Weller, Simon A.
Williamson, Diane
Laws, Thomas R.
Garcia-Dorival, Isabel
Hiscox, Julian
Holder, Benjamin P.
Beauchemin, Catherine A. A.
Perelson, Alan S.
Lopez-Garcia, Martin
Lythe, Grant
Barr, John
Molina-Paris, Carmen
contents 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 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 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.
format Preprint
id arxiv_https___arxiv_org_abs_2010_09898
institution arXiv
publishDate 2020
record_format arxiv
spellingShingle Quantification of Ebola virus replication kinetics in vitro
Liao, Laura E.
Carruthers, Jonathan
Smither, Sophie J.
Team, CL4 Virology
Weller, Simon A.
Williamson, Diane
Laws, Thomas R.
Garcia-Dorival, Isabel
Hiscox, Julian
Holder, Benjamin P.
Beauchemin, Catherine A. A.
Perelson, Alan S.
Lopez-Garcia, Martin
Lythe, Grant
Barr, John
Molina-Paris, Carmen
Cell Behavior
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 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 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.
title Quantification of Ebola virus replication kinetics in vitro
topic Cell Behavior
url https://arxiv.org/abs/2010.09898