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Sendai virus intra-host population dynamics and host immunocompetence influence viral virulence during in vivo passage

In vivo serial passage of non-pathogenic viruses has been shown to lead to increased viral virulence, and although the precise mechanism(s) are not clear, it is known that both host and viral factors are associated with increased pathogenicity. Under- or overnutrition leads to a decreased or dysregu...

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Autores principales: Peña, José, Chen-Harris, Haiyin, Allen, Jonathan E., Hwang, Mona, Elsheikh, Maher, Mabery, Shalini, Bielefeldt-Ohmann, Helle, Zemla, Adam T., Bowen, Richard A., Borucki, Monica K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4989884/
https://www.ncbi.nlm.nih.gov/pubmed/27774301
http://dx.doi.org/10.1093/ve/vew008
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author Peña, José
Chen-Harris, Haiyin
Allen, Jonathan E.
Hwang, Mona
Elsheikh, Maher
Mabery, Shalini
Bielefeldt-Ohmann, Helle
Zemla, Adam T.
Bowen, Richard A.
Borucki, Monica K.
author_facet Peña, José
Chen-Harris, Haiyin
Allen, Jonathan E.
Hwang, Mona
Elsheikh, Maher
Mabery, Shalini
Bielefeldt-Ohmann, Helle
Zemla, Adam T.
Bowen, Richard A.
Borucki, Monica K.
author_sort Peña, José
collection PubMed
description In vivo serial passage of non-pathogenic viruses has been shown to lead to increased viral virulence, and although the precise mechanism(s) are not clear, it is known that both host and viral factors are associated with increased pathogenicity. Under- or overnutrition leads to a decreased or dysregulated immune response and can increase viral mutant spectrum diversity and virulence. The objective of this study was to identify the role of viral mutant spectra dynamics and host immunocompetence in the development of pathogenicity during in vivo passage. Because the nutritional status of the host has been shown to affect the development of viral virulence, the diet of animal model reflected two extremes of diets which exist in the global population, malnutrition and obesity. Sendai virus was serially passaged in groups of mice with differing nutritional status followed by transmission of the passaged virus to a second host species, guinea pigs. Viral population dynamics were characterized using deep sequence analysis and computational modeling. Histopathology, viral titer and cytokine assays were used to characterize viral virulence. Viral virulence increased with passage and the virulent phenotype persisted upon passage to a second host species. Additionally, nutritional status of mice during passage influenced the phenotype. Sequencing revealed the presence of several non-synonymous changes in the consensus sequence associated with passage, a majority of which occurred in the hemagglutinin-neuraminidase and polymerase genes, as well as the presence of persistent high frequency variants in the viral population. In particular, an N1124D change in the consensus sequences of the polymerase gene was detected by passage 10 in a majority of the animals. In vivo comparison of an 1124D plaque isolate to a clone with 1124N genotype indicated that 1124D was associated with increased virulence.
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spelling pubmed-49898842016-10-21 Sendai virus intra-host population dynamics and host immunocompetence influence viral virulence during in vivo passage Peña, José Chen-Harris, Haiyin Allen, Jonathan E. Hwang, Mona Elsheikh, Maher Mabery, Shalini Bielefeldt-Ohmann, Helle Zemla, Adam T. Bowen, Richard A. Borucki, Monica K. Virus Evol Research Article In vivo serial passage of non-pathogenic viruses has been shown to lead to increased viral virulence, and although the precise mechanism(s) are not clear, it is known that both host and viral factors are associated with increased pathogenicity. Under- or overnutrition leads to a decreased or dysregulated immune response and can increase viral mutant spectrum diversity and virulence. The objective of this study was to identify the role of viral mutant spectra dynamics and host immunocompetence in the development of pathogenicity during in vivo passage. Because the nutritional status of the host has been shown to affect the development of viral virulence, the diet of animal model reflected two extremes of diets which exist in the global population, malnutrition and obesity. Sendai virus was serially passaged in groups of mice with differing nutritional status followed by transmission of the passaged virus to a second host species, guinea pigs. Viral population dynamics were characterized using deep sequence analysis and computational modeling. Histopathology, viral titer and cytokine assays were used to characterize viral virulence. Viral virulence increased with passage and the virulent phenotype persisted upon passage to a second host species. Additionally, nutritional status of mice during passage influenced the phenotype. Sequencing revealed the presence of several non-synonymous changes in the consensus sequence associated with passage, a majority of which occurred in the hemagglutinin-neuraminidase and polymerase genes, as well as the presence of persistent high frequency variants in the viral population. In particular, an N1124D change in the consensus sequences of the polymerase gene was detected by passage 10 in a majority of the animals. In vivo comparison of an 1124D plaque isolate to a clone with 1124N genotype indicated that 1124D was associated with increased virulence. Oxford University Press 2016-04-09 /pmc/articles/PMC4989884/ /pubmed/27774301 http://dx.doi.org/10.1093/ve/vew008 Text en © The Author 2016. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Research Article
Peña, José
Chen-Harris, Haiyin
Allen, Jonathan E.
Hwang, Mona
Elsheikh, Maher
Mabery, Shalini
Bielefeldt-Ohmann, Helle
Zemla, Adam T.
Bowen, Richard A.
Borucki, Monica K.
Sendai virus intra-host population dynamics and host immunocompetence influence viral virulence during in vivo passage
title Sendai virus intra-host population dynamics and host immunocompetence influence viral virulence during in vivo passage
title_full Sendai virus intra-host population dynamics and host immunocompetence influence viral virulence during in vivo passage
title_fullStr Sendai virus intra-host population dynamics and host immunocompetence influence viral virulence during in vivo passage
title_full_unstemmed Sendai virus intra-host population dynamics and host immunocompetence influence viral virulence during in vivo passage
title_short Sendai virus intra-host population dynamics and host immunocompetence influence viral virulence during in vivo passage
title_sort sendai virus intra-host population dynamics and host immunocompetence influence viral virulence during in vivo passage
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4989884/
https://www.ncbi.nlm.nih.gov/pubmed/27774301
http://dx.doi.org/10.1093/ve/vew008
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