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Modeling Challenges of Ebola Virus–Host Dynamics during Infection and Treatment

Mathematical modeling of Ebola virus (EBOV)–host dynamics during infection and treatment in vivo is in its infancy due to few studies with frequent viral kinetic data, lack of approved antiviral therapies, and limited insight into the timing of EBOV infection of cells and tissues throughout the body...

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Autores principales: Chertow, Daniel S., Shekhtman, Louis, Lurie, Yoav, Davey, Richard T., Heller, Theo, Dahari, Harel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019702/
https://www.ncbi.nlm.nih.gov/pubmed/31963118
http://dx.doi.org/10.3390/v12010106
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author Chertow, Daniel S.
Shekhtman, Louis
Lurie, Yoav
Davey, Richard T.
Heller, Theo
Dahari, Harel
author_facet Chertow, Daniel S.
Shekhtman, Louis
Lurie, Yoav
Davey, Richard T.
Heller, Theo
Dahari, Harel
author_sort Chertow, Daniel S.
collection PubMed
description Mathematical modeling of Ebola virus (EBOV)–host dynamics during infection and treatment in vivo is in its infancy due to few studies with frequent viral kinetic data, lack of approved antiviral therapies, and limited insight into the timing of EBOV infection of cells and tissues throughout the body. Current in-host mathematical models simplify EBOV infection by assuming a single homogeneous compartment of infection. In particular, a recent modeling study assumed the liver as the largest solid organ targeted by EBOV infection and predicted that nearly all cells become refractory to infection within seven days of initial infection without antiviral treatment. We compared our observations of EBOV kinetics in multiple anatomic compartments and hepatocellular injury in a critically ill patient with Ebola virus disease (EVD) with this model’s predictions. We also explored the model’s predictions, with and without antiviral therapy, by recapitulating the model using published inputs and assumptions. Our findings highlight the challenges of modeling EBOV–host dynamics and therapeutic efficacy and emphasize the need for iterative interdisciplinary efforts to refine mathematical models that might advance understanding of EVD pathogenesis and treatment.
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spelling pubmed-70197022020-03-09 Modeling Challenges of Ebola Virus–Host Dynamics during Infection and Treatment Chertow, Daniel S. Shekhtman, Louis Lurie, Yoav Davey, Richard T. Heller, Theo Dahari, Harel Viruses Article Mathematical modeling of Ebola virus (EBOV)–host dynamics during infection and treatment in vivo is in its infancy due to few studies with frequent viral kinetic data, lack of approved antiviral therapies, and limited insight into the timing of EBOV infection of cells and tissues throughout the body. Current in-host mathematical models simplify EBOV infection by assuming a single homogeneous compartment of infection. In particular, a recent modeling study assumed the liver as the largest solid organ targeted by EBOV infection and predicted that nearly all cells become refractory to infection within seven days of initial infection without antiviral treatment. We compared our observations of EBOV kinetics in multiple anatomic compartments and hepatocellular injury in a critically ill patient with Ebola virus disease (EVD) with this model’s predictions. We also explored the model’s predictions, with and without antiviral therapy, by recapitulating the model using published inputs and assumptions. Our findings highlight the challenges of modeling EBOV–host dynamics and therapeutic efficacy and emphasize the need for iterative interdisciplinary efforts to refine mathematical models that might advance understanding of EVD pathogenesis and treatment. MDPI 2020-01-16 /pmc/articles/PMC7019702/ /pubmed/31963118 http://dx.doi.org/10.3390/v12010106 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chertow, Daniel S.
Shekhtman, Louis
Lurie, Yoav
Davey, Richard T.
Heller, Theo
Dahari, Harel
Modeling Challenges of Ebola Virus–Host Dynamics during Infection and Treatment
title Modeling Challenges of Ebola Virus–Host Dynamics during Infection and Treatment
title_full Modeling Challenges of Ebola Virus–Host Dynamics during Infection and Treatment
title_fullStr Modeling Challenges of Ebola Virus–Host Dynamics during Infection and Treatment
title_full_unstemmed Modeling Challenges of Ebola Virus–Host Dynamics during Infection and Treatment
title_short Modeling Challenges of Ebola Virus–Host Dynamics during Infection and Treatment
title_sort modeling challenges of ebola virus–host dynamics during infection and treatment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019702/
https://www.ncbi.nlm.nih.gov/pubmed/31963118
http://dx.doi.org/10.3390/v12010106
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