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The effect of random virus failure following cell entry on infection outcome and the success of antiviral therapy

A virus infection can be initiated with very few or even a single infectious virion, and as such can become extinct, i.e. stochastically fail to take hold or spread significantly. There are many ways that a fully competent infectious virion, having successfully entered a cell, can fail to cause a pr...

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Autores principales: Quirouette, Christian, Cresta, Daniel, Li, Jizhou, Wilkie, Kathleen P., Liang, Haozhao, Beauchemin, Catherine A. A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10567758/
https://www.ncbi.nlm.nih.gov/pubmed/37821517
http://dx.doi.org/10.1038/s41598-023-44180-w
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author Quirouette, Christian
Cresta, Daniel
Li, Jizhou
Wilkie, Kathleen P.
Liang, Haozhao
Beauchemin, Catherine A. A.
author_facet Quirouette, Christian
Cresta, Daniel
Li, Jizhou
Wilkie, Kathleen P.
Liang, Haozhao
Beauchemin, Catherine A. A.
author_sort Quirouette, Christian
collection PubMed
description A virus infection can be initiated with very few or even a single infectious virion, and as such can become extinct, i.e. stochastically fail to take hold or spread significantly. There are many ways that a fully competent infectious virion, having successfully entered a cell, can fail to cause a productive infection, i.e. one that yields infectious virus progeny. Though many stochastic models (SMs) have been developed and used to estimate a virus infection’s establishment probability, these typically neglect infection failure post virus entry. The SM presented herein introduces parameter [Formula: see text] which corresponds to the probability that a virion’s entry into a cell will result in a productive cell infection. We derive an expression for the likelihood of infection establishment in this new SM, and find that prophylactic therapy with an antiviral reducing [Formula: see text] is at least as good or better at decreasing the establishment probability, compared to antivirals reducing the rates of virus production or virus entry into cells, irrespective of the SM parameters. We investigate the difference in the fraction of cells consumed by so-called extinct versus established virus infections, and find that this distinction becomes biologically meaningless as the probability of establishment approaches zero. We explain why the release of virions continuously over an infectious cell’s lifespan, rather than as a single burst at the end of the cell’s lifespan, does not result in an increased risk of infection extinction. We show, instead, that the number of virus released, not the timing of the release, affects infection establishment and associated critical antiviral efficacy.
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spelling pubmed-105677582023-10-13 The effect of random virus failure following cell entry on infection outcome and the success of antiviral therapy Quirouette, Christian Cresta, Daniel Li, Jizhou Wilkie, Kathleen P. Liang, Haozhao Beauchemin, Catherine A. A. Sci Rep Article A virus infection can be initiated with very few or even a single infectious virion, and as such can become extinct, i.e. stochastically fail to take hold or spread significantly. There are many ways that a fully competent infectious virion, having successfully entered a cell, can fail to cause a productive infection, i.e. one that yields infectious virus progeny. Though many stochastic models (SMs) have been developed and used to estimate a virus infection’s establishment probability, these typically neglect infection failure post virus entry. The SM presented herein introduces parameter [Formula: see text] which corresponds to the probability that a virion’s entry into a cell will result in a productive cell infection. We derive an expression for the likelihood of infection establishment in this new SM, and find that prophylactic therapy with an antiviral reducing [Formula: see text] is at least as good or better at decreasing the establishment probability, compared to antivirals reducing the rates of virus production or virus entry into cells, irrespective of the SM parameters. We investigate the difference in the fraction of cells consumed by so-called extinct versus established virus infections, and find that this distinction becomes biologically meaningless as the probability of establishment approaches zero. We explain why the release of virions continuously over an infectious cell’s lifespan, rather than as a single burst at the end of the cell’s lifespan, does not result in an increased risk of infection extinction. We show, instead, that the number of virus released, not the timing of the release, affects infection establishment and associated critical antiviral efficacy. Nature Publishing Group UK 2023-10-11 /pmc/articles/PMC10567758/ /pubmed/37821517 http://dx.doi.org/10.1038/s41598-023-44180-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Quirouette, Christian
Cresta, Daniel
Li, Jizhou
Wilkie, Kathleen P.
Liang, Haozhao
Beauchemin, Catherine A. A.
The effect of random virus failure following cell entry on infection outcome and the success of antiviral therapy
title The effect of random virus failure following cell entry on infection outcome and the success of antiviral therapy
title_full The effect of random virus failure following cell entry on infection outcome and the success of antiviral therapy
title_fullStr The effect of random virus failure following cell entry on infection outcome and the success of antiviral therapy
title_full_unstemmed The effect of random virus failure following cell entry on infection outcome and the success of antiviral therapy
title_short The effect of random virus failure following cell entry on infection outcome and the success of antiviral therapy
title_sort effect of random virus failure following cell entry on infection outcome and the success of antiviral therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10567758/
https://www.ncbi.nlm.nih.gov/pubmed/37821517
http://dx.doi.org/10.1038/s41598-023-44180-w
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