PD-1 of Sigmodon hispidus: Gene identification, characterization and preliminary evaluation of expression in inactivated RSV vaccine-induced enhanced respiratory disease

Abstract Sigmodon hispidus or cotton rat is an excellent animal model for studying human infections of respiratory viruses including respiratory syncytial virus (RSV), which is the leading cause of hospitalization in infants and causes high rates of infection in the elderly and immunocompromised pat...

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Autores principales: Abenaya Muralidharan, Louise Larocque, Marsha Russell, Marybeth Creskey, Changgui Li, Wangxue Chen, Gary Van Domselaar, Jingxin Cao, Terry Cyr, Michael Rosu-Myles, Lisheng Wang, Xuguang Li
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Publicado: Nature Portfolio 2019
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Acceso en línea:https://doaj.org/article/e40d9815733c4271aa9e178757463077
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spelling oai:doaj.org-article:e40d9815733c4271aa9e1787574630772021-12-02T16:08:04ZPD-1 of Sigmodon hispidus: Gene identification, characterization and preliminary evaluation of expression in inactivated RSV vaccine-induced enhanced respiratory disease10.1038/s41598-019-48225-x2045-2322https://doaj.org/article/e40d9815733c4271aa9e1787574630772019-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-48225-xhttps://doaj.org/toc/2045-2322Abstract Sigmodon hispidus or cotton rat is an excellent animal model for studying human infections of respiratory viruses including respiratory syncytial virus (RSV), which is the leading cause of hospitalization in infants and causes high rates of infection in the elderly and immunocompromised patient populations. Despite several decades of research, no vaccine has been licensed whereas inactivated vaccines have been shown to induce severe adverse reaction in a clinical trial, with other forms of RSV vaccine also found to induce enhanced disease in preclinical animal studies. While arguably the cotton rat is the best small animal model for evaluation of RSV vaccines and antivirals, many important genes of the immune system remain to be isolated. Programmed cell death-1 (PD-1) plays an integral role in regulating many aspects of immunity by inducing suppressive signals. In this study, we report the isolation of mRNA encoding the cotton rat PD-1 (crPD-1) and characterization of the PD-1 protein. crPD-1 bound to its cognate ligand on dendritic cells and effectively suppressed cytokine secretion. Moreover, using the newly acquired gene sequence, we observed a decreased level of crPD-1 levels in cotton rats with enhanced respiratory disease induced by inactivated RSV vaccine, unraveling a new facet of vaccine-induced disease.Abenaya MuralidharanLouise LarocqueMarsha RussellMarybeth CreskeyChanggui LiWangxue ChenGary Van DomselaarJingxin CaoTerry CyrMichael Rosu-MylesLisheng WangXuguang LiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-12 (2019)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Abenaya Muralidharan
Louise Larocque
Marsha Russell
Marybeth Creskey
Changgui Li
Wangxue Chen
Gary Van Domselaar
Jingxin Cao
Terry Cyr
Michael Rosu-Myles
Lisheng Wang
Xuguang Li
PD-1 of Sigmodon hispidus: Gene identification, characterization and preliminary evaluation of expression in inactivated RSV vaccine-induced enhanced respiratory disease
description Abstract Sigmodon hispidus or cotton rat is an excellent animal model for studying human infections of respiratory viruses including respiratory syncytial virus (RSV), which is the leading cause of hospitalization in infants and causes high rates of infection in the elderly and immunocompromised patient populations. Despite several decades of research, no vaccine has been licensed whereas inactivated vaccines have been shown to induce severe adverse reaction in a clinical trial, with other forms of RSV vaccine also found to induce enhanced disease in preclinical animal studies. While arguably the cotton rat is the best small animal model for evaluation of RSV vaccines and antivirals, many important genes of the immune system remain to be isolated. Programmed cell death-1 (PD-1) plays an integral role in regulating many aspects of immunity by inducing suppressive signals. In this study, we report the isolation of mRNA encoding the cotton rat PD-1 (crPD-1) and characterization of the PD-1 protein. crPD-1 bound to its cognate ligand on dendritic cells and effectively suppressed cytokine secretion. Moreover, using the newly acquired gene sequence, we observed a decreased level of crPD-1 levels in cotton rats with enhanced respiratory disease induced by inactivated RSV vaccine, unraveling a new facet of vaccine-induced disease.
format article
author Abenaya Muralidharan
Louise Larocque
Marsha Russell
Marybeth Creskey
Changgui Li
Wangxue Chen
Gary Van Domselaar
Jingxin Cao
Terry Cyr
Michael Rosu-Myles
Lisheng Wang
Xuguang Li
author_facet Abenaya Muralidharan
Louise Larocque
Marsha Russell
Marybeth Creskey
Changgui Li
Wangxue Chen
Gary Van Domselaar
Jingxin Cao
Terry Cyr
Michael Rosu-Myles
Lisheng Wang
Xuguang Li
author_sort Abenaya Muralidharan
title PD-1 of Sigmodon hispidus: Gene identification, characterization and preliminary evaluation of expression in inactivated RSV vaccine-induced enhanced respiratory disease
title_short PD-1 of Sigmodon hispidus: Gene identification, characterization and preliminary evaluation of expression in inactivated RSV vaccine-induced enhanced respiratory disease
title_full PD-1 of Sigmodon hispidus: Gene identification, characterization and preliminary evaluation of expression in inactivated RSV vaccine-induced enhanced respiratory disease
title_fullStr PD-1 of Sigmodon hispidus: Gene identification, characterization and preliminary evaluation of expression in inactivated RSV vaccine-induced enhanced respiratory disease
title_full_unstemmed PD-1 of Sigmodon hispidus: Gene identification, characterization and preliminary evaluation of expression in inactivated RSV vaccine-induced enhanced respiratory disease
title_sort pd-1 of sigmodon hispidus: gene identification, characterization and preliminary evaluation of expression in inactivated rsv vaccine-induced enhanced respiratory disease
publisher Nature Portfolio
publishDate 2019
url https://doaj.org/article/e40d9815733c4271aa9e178757463077
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