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Within-Host Phenotypic Evolution and the Population-Level Control of Chronic Viral Infections by Treatment and Prophylaxis

Chronic viral infections can persist for decades spanning thousands of viral generations, leading to a highly diverse population of viruses with its own complex evolutionary history. We propose an expandable mathematical framework for understanding how the emergence of genetic and phenotypic diversi...

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Autores principales: Gromov, Dmitry, Romero-Severson, Ethan O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274820/
https://www.ncbi.nlm.nih.gov/pubmed/34258245
http://dx.doi.org/10.3390/math8091500
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author Gromov, Dmitry
Romero-Severson, Ethan O.
author_facet Gromov, Dmitry
Romero-Severson, Ethan O.
author_sort Gromov, Dmitry
collection PubMed
description Chronic viral infections can persist for decades spanning thousands of viral generations, leading to a highly diverse population of viruses with its own complex evolutionary history. We propose an expandable mathematical framework for understanding how the emergence of genetic and phenotypic diversity affects the population-level control of those infections by both non-curative treatment and chemo-prophylactic measures. Our frameworks allows both neutral and phenotypic evolution, and we consider the specific evolution of contagiousness, resistance to therapy, and efficacy of prophylaxis. We compute both the controlled and uncontrolled, population-level basic reproduction number accounting for the within-host evolutionary process where new phenotypes emerge and are lost in infected persons, which we also extend to include both treatment and prophylactic control efforts. We used these results to discuss the conditions under which the relative efficacy of prophylactic versus therapeutic methods of control are superior. Finally, we give expressions for the endemic equilibrium of these models for certain constrained versions of the within-host evolutionary model providing a potential method for estimating within-host evolutionary parameters from population-level genetic sequence data.
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spelling pubmed-82748202021-07-12 Within-Host Phenotypic Evolution and the Population-Level Control of Chronic Viral Infections by Treatment and Prophylaxis Gromov, Dmitry Romero-Severson, Ethan O. Mathematics (Basel) Article Chronic viral infections can persist for decades spanning thousands of viral generations, leading to a highly diverse population of viruses with its own complex evolutionary history. We propose an expandable mathematical framework for understanding how the emergence of genetic and phenotypic diversity affects the population-level control of those infections by both non-curative treatment and chemo-prophylactic measures. Our frameworks allows both neutral and phenotypic evolution, and we consider the specific evolution of contagiousness, resistance to therapy, and efficacy of prophylaxis. We compute both the controlled and uncontrolled, population-level basic reproduction number accounting for the within-host evolutionary process where new phenotypes emerge and are lost in infected persons, which we also extend to include both treatment and prophylactic control efforts. We used these results to discuss the conditions under which the relative efficacy of prophylactic versus therapeutic methods of control are superior. Finally, we give expressions for the endemic equilibrium of these models for certain constrained versions of the within-host evolutionary model providing a potential method for estimating within-host evolutionary parameters from population-level genetic sequence data. 2020-09-04 2020-09 /pmc/articles/PMC8274820/ /pubmed/34258245 http://dx.doi.org/10.3390/math8091500 Text en https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Gromov, Dmitry
Romero-Severson, Ethan O.
Within-Host Phenotypic Evolution and the Population-Level Control of Chronic Viral Infections by Treatment and Prophylaxis
title Within-Host Phenotypic Evolution and the Population-Level Control of Chronic Viral Infections by Treatment and Prophylaxis
title_full Within-Host Phenotypic Evolution and the Population-Level Control of Chronic Viral Infections by Treatment and Prophylaxis
title_fullStr Within-Host Phenotypic Evolution and the Population-Level Control of Chronic Viral Infections by Treatment and Prophylaxis
title_full_unstemmed Within-Host Phenotypic Evolution and the Population-Level Control of Chronic Viral Infections by Treatment and Prophylaxis
title_short Within-Host Phenotypic Evolution and the Population-Level Control of Chronic Viral Infections by Treatment and Prophylaxis
title_sort within-host phenotypic evolution and the population-level control of chronic viral infections by treatment and prophylaxis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274820/
https://www.ncbi.nlm.nih.gov/pubmed/34258245
http://dx.doi.org/10.3390/math8091500
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