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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0265094 |
| _version_ | 1818195837557145600 |
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| author | Terri J Harford Fariba Rezaee Briana R Dye Jia Fan Jason R Spence Giovanni Piedimonte |
| author_facet | Terri J Harford Fariba Rezaee Briana R Dye Jia Fan Jason R Spence Giovanni Piedimonte |
| author_sort | Terri J Harford |
| collection | DOAJ |
| 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 1st 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 (TRPV1) 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. |
| first_indexed | 2024-12-12T01:24:32Z |
| format | Article |
| id | doaj.art-1e284db4f2304ef0b563ddfaf755e4f4 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T01:24:32Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-1e284db4f2304ef0b563ddfaf755e4f42022-12-22T00:43:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01173e026509410.1371/journal.pone.0265094RSV-induced changes in a 3-dimensional organoid model of human fetal lungs.Terri J HarfordFariba RezaeeBriana R DyeJia FanJason R SpenceGiovanni PiedimonteWe 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 1st 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 (TRPV1) 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.https://doi.org/10.1371/journal.pone.0265094 |
| spellingShingle | Terri J Harford Fariba Rezaee Briana R Dye Jia Fan Jason R Spence Giovanni Piedimonte RSV-induced changes in a 3-dimensional organoid model of human fetal lungs. PLoS ONE |
| 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 |
| url | https://doi.org/10.1371/journal.pone.0265094 |
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