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Reducing Uncertainty in Within-Host Parameter Estimates of Influenza Infection by Measuring Both Infectious and Total Viral Load
For in vivo studies of influenza dynamics where within-host measurements are fit with a mathematical model, infectivity assays (e.g. 50% tissue culture infectious dose; TCID(50)) are often used to estimate the infectious virion concentration over time. Less frequently, measurements of the total (inf...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655064/ https://www.ncbi.nlm.nih.gov/pubmed/23691157 http://dx.doi.org/10.1371/journal.pone.0064098 |
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author | Petrie, Stephen M. Guarnaccia, Teagan Laurie, Karen L. Hurt, Aeron C. McVernon, Jodie McCaw, James M. |
author_facet | Petrie, Stephen M. Guarnaccia, Teagan Laurie, Karen L. Hurt, Aeron C. McVernon, Jodie McCaw, James M. |
author_sort | Petrie, Stephen M. |
collection | PubMed |
description | For in vivo studies of influenza dynamics where within-host measurements are fit with a mathematical model, infectivity assays (e.g. 50% tissue culture infectious dose; TCID(50)) are often used to estimate the infectious virion concentration over time. Less frequently, measurements of the total (infectious and non-infectious) viral particle concentration (obtained using real-time reverse transcription-polymerase chain reaction; rRT-PCR) have been used as an alternative to infectivity assays. We investigated the degree to which measuring both infectious (via TCID(50)) and total (via rRT-PCR) viral load allows within-host model parameters to be estimated with greater consistency and reduced uncertainty, compared with fitting to TCID(50) data alone. We applied our models to viral load data from an experimental ferret infection study. Best-fit parameter estimates for the “dual-measurement” model are similar to those from the TCID(50)-only model, with greater consistency in best-fit estimates across different experiments, as well as reduced uncertainty in some parameter estimates. Our results also highlight how variation in TCID(50) assay sensitivity and calibration may hinder model interpretation, as some parameter estimates systematically vary with known uncontrolled variations in the assay. Our techniques may aid in drawing stronger quantitative inferences from in vivo studies of influenza virus dynamics. |
format | Online Article Text |
id | pubmed-3655064 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-36550642013-05-20 Reducing Uncertainty in Within-Host Parameter Estimates of Influenza Infection by Measuring Both Infectious and Total Viral Load Petrie, Stephen M. Guarnaccia, Teagan Laurie, Karen L. Hurt, Aeron C. McVernon, Jodie McCaw, James M. PLoS One Research Article For in vivo studies of influenza dynamics where within-host measurements are fit with a mathematical model, infectivity assays (e.g. 50% tissue culture infectious dose; TCID(50)) are often used to estimate the infectious virion concentration over time. Less frequently, measurements of the total (infectious and non-infectious) viral particle concentration (obtained using real-time reverse transcription-polymerase chain reaction; rRT-PCR) have been used as an alternative to infectivity assays. We investigated the degree to which measuring both infectious (via TCID(50)) and total (via rRT-PCR) viral load allows within-host model parameters to be estimated with greater consistency and reduced uncertainty, compared with fitting to TCID(50) data alone. We applied our models to viral load data from an experimental ferret infection study. Best-fit parameter estimates for the “dual-measurement” model are similar to those from the TCID(50)-only model, with greater consistency in best-fit estimates across different experiments, as well as reduced uncertainty in some parameter estimates. Our results also highlight how variation in TCID(50) assay sensitivity and calibration may hinder model interpretation, as some parameter estimates systematically vary with known uncontrolled variations in the assay. Our techniques may aid in drawing stronger quantitative inferences from in vivo studies of influenza virus dynamics. Public Library of Science 2013-05-15 /pmc/articles/PMC3655064/ /pubmed/23691157 http://dx.doi.org/10.1371/journal.pone.0064098 Text en © 2013 Petrie et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Petrie, Stephen M. Guarnaccia, Teagan Laurie, Karen L. Hurt, Aeron C. McVernon, Jodie McCaw, James M. Reducing Uncertainty in Within-Host Parameter Estimates of Influenza Infection by Measuring Both Infectious and Total Viral Load |
title | Reducing Uncertainty in Within-Host Parameter Estimates of Influenza Infection by Measuring Both Infectious and Total Viral Load |
title_full | Reducing Uncertainty in Within-Host Parameter Estimates of Influenza Infection by Measuring Both Infectious and Total Viral Load |
title_fullStr | Reducing Uncertainty in Within-Host Parameter Estimates of Influenza Infection by Measuring Both Infectious and Total Viral Load |
title_full_unstemmed | Reducing Uncertainty in Within-Host Parameter Estimates of Influenza Infection by Measuring Both Infectious and Total Viral Load |
title_short | Reducing Uncertainty in Within-Host Parameter Estimates of Influenza Infection by Measuring Both Infectious and Total Viral Load |
title_sort | reducing uncertainty in within-host parameter estimates of influenza infection by measuring both infectious and total viral load |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655064/ https://www.ncbi.nlm.nih.gov/pubmed/23691157 http://dx.doi.org/10.1371/journal.pone.0064098 |
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