Quantifying dose-, strain-, and tissue-specific kinetics of parainfluenza virus infection.

Human parainfluenza viruses (HPIVs) are a leading cause of acute respiratory infection hospitalization in children, yet little is known about how dose, strain, tissue tropism, and individual heterogeneity affects the processes driving growth and clearance kinetics. Longitudinal measurements are poss...

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Autores principales:	Lubna Pinky, Crystal W Burke, Charles J Russell, Amber M Smith
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/d3c9ec477df046dcad760f539c2dad11
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spelling	oai:doaj.org-article:d3c9ec477df046dcad760f539c2dad112021-12-02T19:58:05ZQuantifying dose-, strain-, and tissue-specific kinetics of parainfluenza virus infection.1553-734X1553-735810.1371/journal.pcbi.1009299https://doaj.org/article/d3c9ec477df046dcad760f539c2dad112021-08-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.1009299https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Human parainfluenza viruses (HPIVs) are a leading cause of acute respiratory infection hospitalization in children, yet little is known about how dose, strain, tissue tropism, and individual heterogeneity affects the processes driving growth and clearance kinetics. Longitudinal measurements are possible by using reporter Sendai viruses, the murine counterpart of HPIV 1, that express luciferase, where the insertion location yields a wild-type (rSeV-luc(M-F)) or attenuated (rSeV-luc(P-M)) phenotype. Bioluminescence from individual animals suggests that there is a rapid increase in expression followed by a peak, biphasic clearance, and resolution. However, these kinetics vary between individuals and with dose, strain, and whether the infection was initiated in the upper and/or lower respiratory tract. To quantify the differences, we translated the bioluminescence measurements from the nasopharynx, trachea, and lung into viral loads and used a mathematical model together a nonlinear mixed effects approach to define the mechanisms distinguishing each scenario. The results confirmed a higher rate of virus production with the rSeV-luc(M-F) virus compared to its attenuated counterpart, and suggested that low doses result in disproportionately fewer infected cells. The analyses indicated faster infectivity and infected cell clearance rates in the lung and that higher viral doses, and concomitantly higher infected cell numbers, resulted in more rapid clearance. This parameter was also highly variable amongst individuals, which was particularly evident during infection in the lung. These critical differences provide important insight into distinct HPIV dynamics, and show how bioluminescence data can be combined with quantitative analyses to dissect host-, virus-, and dose-dependent effects.Lubna PinkyCrystal W BurkeCharles J RussellAmber M SmithPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 17, Iss 8, p e1009299 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Lubna Pinky Crystal W Burke Charles J Russell Amber M Smith Quantifying dose-, strain-, and tissue-specific kinetics of parainfluenza virus infection.
description	Human parainfluenza viruses (HPIVs) are a leading cause of acute respiratory infection hospitalization in children, yet little is known about how dose, strain, tissue tropism, and individual heterogeneity affects the processes driving growth and clearance kinetics. Longitudinal measurements are possible by using reporter Sendai viruses, the murine counterpart of HPIV 1, that express luciferase, where the insertion location yields a wild-type (rSeV-luc(M-F)) or attenuated (rSeV-luc(P-M)) phenotype. Bioluminescence from individual animals suggests that there is a rapid increase in expression followed by a peak, biphasic clearance, and resolution. However, these kinetics vary between individuals and with dose, strain, and whether the infection was initiated in the upper and/or lower respiratory tract. To quantify the differences, we translated the bioluminescence measurements from the nasopharynx, trachea, and lung into viral loads and used a mathematical model together a nonlinear mixed effects approach to define the mechanisms distinguishing each scenario. The results confirmed a higher rate of virus production with the rSeV-luc(M-F) virus compared to its attenuated counterpart, and suggested that low doses result in disproportionately fewer infected cells. The analyses indicated faster infectivity and infected cell clearance rates in the lung and that higher viral doses, and concomitantly higher infected cell numbers, resulted in more rapid clearance. This parameter was also highly variable amongst individuals, which was particularly evident during infection in the lung. These critical differences provide important insight into distinct HPIV dynamics, and show how bioluminescence data can be combined with quantitative analyses to dissect host-, virus-, and dose-dependent effects.
format	article
author	Lubna Pinky Crystal W Burke Charles J Russell Amber M Smith
author_facet	Lubna Pinky Crystal W Burke Charles J Russell Amber M Smith
author_sort	Lubna Pinky
title	Quantifying dose-, strain-, and tissue-specific kinetics of parainfluenza virus infection.
title_short	Quantifying dose-, strain-, and tissue-specific kinetics of parainfluenza virus infection.
title_full	Quantifying dose-, strain-, and tissue-specific kinetics of parainfluenza virus infection.
title_fullStr	Quantifying dose-, strain-, and tissue-specific kinetics of parainfluenza virus infection.
title_full_unstemmed	Quantifying dose-, strain-, and tissue-specific kinetics of parainfluenza virus infection.
title_sort	quantifying dose-, strain-, and tissue-specific kinetics of parainfluenza virus infection.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/d3c9ec477df046dcad760f539c2dad11
work_keys_str_mv	AT lubnapinky quantifyingdosestrainandtissuespecifickineticsofparainfluenzavirusinfection AT crystalwburke quantifyingdosestrainandtissuespecifickineticsofparainfluenzavirusinfection AT charlesjrussell quantifyingdosestrainandtissuespecifickineticsofparainfluenzavirusinfection AT ambermsmith quantifyingdosestrainandtissuespecifickineticsofparainfluenzavirusinfection
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Quantifying dose-, strain-, and tissue-specific kinetics of parainfluenza virus infection.

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