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RSV-induced changes in a 3-dimensional organoid model of human fetal lungs

We have shown that respiratory syncytial virus (RSV) can spread hematogenously from infected airways of a pregnant woman to the developing fetal lungs in utero. This study sought to measure RSV replication, cytopathic effects, and protein expression in human lung organoids (HLOs) reproducing archite...

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Autores principales: Harford, Terri J., Rezaee, Fariba, Dye, Briana R., Fan, Jia, Spence, Jason R., Piedimonte, Giovanni
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8906588/
https://www.ncbi.nlm.nih.gov/pubmed/35263387
http://dx.doi.org/10.1371/journal.pone.0265094
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author Harford, Terri J.
Rezaee, Fariba
Dye, Briana R.
Fan, Jia
Spence, Jason R.
Piedimonte, Giovanni
author_facet Harford, Terri J.
Rezaee, Fariba
Dye, Briana R.
Fan, Jia
Spence, Jason R.
Piedimonte, Giovanni
author_sort Harford, Terri J.
collection PubMed
description We have shown that respiratory syncytial virus (RSV) can spread hematogenously from infected airways of a pregnant woman to the developing fetal lungs in utero. This study sought to measure RSV replication, cytopathic effects, and protein expression in human lung organoids (HLOs) reproducing architecture and transcriptional profiles of human fetal lungs during the 1(st) trimester of gestation. HLOs derived from human pluripotent stem cells were microinjected after 50 or 100 days in culture with medium or recombinant RSV-A2 expressing the red fluorescent protein gene (rrRSV). Infection was monitored by fluorescent microscopy and PCR. Immunohistochemistry and proteomic analysis were performed. RSV infected HLOs in a dose- and time-dependent manner. RSV-infected HLOs increased expression of CC10 (Club cells), but had sparse FOXJ1 (ciliated cells). Disruption of F-actin cytoskeleton was consistent with proteomic data showing a significant increase in Rho GTPases proteins. RSV upregulated the transient receptor potential vanilloid 1 (TRPV(1)) channel and, while β2 adrenergic receptor (β2AR) expression was decreased overall, its phosphorylated form increased. Our data suggest that prenatal RSV infection produces profound changes in fetal lungs’ architecture and expression profiles and maybe an essential precursor of chronic airway dysfunction. expression profiles, and possibly be an important precursor of chronic airway dysfunction.
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spelling pubmed-89065882022-03-10 RSV-induced changes in a 3-dimensional organoid model of human fetal lungs Harford, Terri J. Rezaee, Fariba Dye, Briana R. Fan, Jia Spence, Jason R. Piedimonte, Giovanni PLoS One Research Article We have shown that respiratory syncytial virus (RSV) can spread hematogenously from infected airways of a pregnant woman to the developing fetal lungs in utero. This study sought to measure RSV replication, cytopathic effects, and protein expression in human lung organoids (HLOs) reproducing architecture and transcriptional profiles of human fetal lungs during the 1(st) trimester of gestation. HLOs derived from human pluripotent stem cells were microinjected after 50 or 100 days in culture with medium or recombinant RSV-A2 expressing the red fluorescent protein gene (rrRSV). Infection was monitored by fluorescent microscopy and PCR. Immunohistochemistry and proteomic analysis were performed. RSV infected HLOs in a dose- and time-dependent manner. RSV-infected HLOs increased expression of CC10 (Club cells), but had sparse FOXJ1 (ciliated cells). Disruption of F-actin cytoskeleton was consistent with proteomic data showing a significant increase in Rho GTPases proteins. RSV upregulated the transient receptor potential vanilloid 1 (TRPV(1)) channel and, while β2 adrenergic receptor (β2AR) expression was decreased overall, its phosphorylated form increased. Our data suggest that prenatal RSV infection produces profound changes in fetal lungs’ architecture and expression profiles and maybe an essential precursor of chronic airway dysfunction. expression profiles, and possibly be an important precursor of chronic airway dysfunction. Public Library of Science 2022-03-09 /pmc/articles/PMC8906588/ /pubmed/35263387 http://dx.doi.org/10.1371/journal.pone.0265094 Text en © 2022 Harford et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Harford, Terri J.
Rezaee, Fariba
Dye, Briana R.
Fan, Jia
Spence, Jason R.
Piedimonte, Giovanni
RSV-induced changes in a 3-dimensional organoid model of human fetal lungs
title RSV-induced changes in a 3-dimensional organoid model of human fetal lungs
title_full RSV-induced changes in a 3-dimensional organoid model of human fetal lungs
title_fullStr RSV-induced changes in a 3-dimensional organoid model of human fetal lungs
title_full_unstemmed RSV-induced changes in a 3-dimensional organoid model of human fetal lungs
title_short RSV-induced changes in a 3-dimensional organoid model of human fetal lungs
title_sort rsv-induced changes in a 3-dimensional organoid model of human fetal lungs
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8906588/
https://www.ncbi.nlm.nih.gov/pubmed/35263387
http://dx.doi.org/10.1371/journal.pone.0265094
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