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Metabolic Reprogramming of Nasal Airway Epithelial Cells Following Infant Respiratory Syncytial Virus Infection
Respiratory syncytial virus (RSV) is a seasonal mucosal pathogen that infects the ciliated respiratory epithelium and results in the most severe morbidity in the first six months of life. RSV is a common cause of acute respiratory infection during infancy and is an important early-life risk factor s...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538412/ https://www.ncbi.nlm.nih.gov/pubmed/34696488 http://dx.doi.org/10.3390/v13102055 |
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author | Connelly, Andrew R. Jeong, Brian M. Coden, Mackenzie E. Cao, Jacob Y. Chirkova, Tatiana Rosas-Salazar, Christian Cephus, Jacqueline-Yvonne Anderson, Larry J. Newcomb, Dawn C. Hartert, Tina V. Berdnikovs, Sergejs |
author_facet | Connelly, Andrew R. Jeong, Brian M. Coden, Mackenzie E. Cao, Jacob Y. Chirkova, Tatiana Rosas-Salazar, Christian Cephus, Jacqueline-Yvonne Anderson, Larry J. Newcomb, Dawn C. Hartert, Tina V. Berdnikovs, Sergejs |
author_sort | Connelly, Andrew R. |
collection | PubMed |
description | Respiratory syncytial virus (RSV) is a seasonal mucosal pathogen that infects the ciliated respiratory epithelium and results in the most severe morbidity in the first six months of life. RSV is a common cause of acute respiratory infection during infancy and is an important early-life risk factor strongly associated with asthma development. While this association has been repeatedly demonstrated, limited progress has been made on the mechanistic understanding in humans of the contribution of infant RSV infection to airway epithelial dysfunction. An active infection of epithelial cells with RSV in vitro results in heightened central metabolism and overall hypermetabolic state; however, little is known about whether natural infection with RSV in vivo results in lasting metabolic reprogramming of the airway epithelium in infancy. To address this gap, we performed functional metabolomics, 13C glucose metabolic flux analysis, and RNA-seq gene expression analysis of nasal airway epithelial cells (NAECs) sampled from infants between 2–3 years of age, with RSV infection or not during the first year of life. We found that RSV infection in infancy was associated with lasting epithelial metabolic reprogramming, which was characterized by (1) significant increase in glucose uptake and differential utilization of glucose by epithelium; (2) altered preferences for metabolism of several carbon and energy sources; and (3) significant sexual dimorphism in metabolic parameters, with RSV-induced metabolic changes most pronounced in male epithelium. In summary, our study supports the proposed phenomenon of metabolic reprogramming of epithelial cells associated with RSV infection in infancy and opens exciting new venues for pursuing mechanisms of RSV-induced epithelial barrier dysfunction in early life. |
format | Online Article Text |
id | pubmed-8538412 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85384122021-10-24 Metabolic Reprogramming of Nasal Airway Epithelial Cells Following Infant Respiratory Syncytial Virus Infection Connelly, Andrew R. Jeong, Brian M. Coden, Mackenzie E. Cao, Jacob Y. Chirkova, Tatiana Rosas-Salazar, Christian Cephus, Jacqueline-Yvonne Anderson, Larry J. Newcomb, Dawn C. Hartert, Tina V. Berdnikovs, Sergejs Viruses Article Respiratory syncytial virus (RSV) is a seasonal mucosal pathogen that infects the ciliated respiratory epithelium and results in the most severe morbidity in the first six months of life. RSV is a common cause of acute respiratory infection during infancy and is an important early-life risk factor strongly associated with asthma development. While this association has been repeatedly demonstrated, limited progress has been made on the mechanistic understanding in humans of the contribution of infant RSV infection to airway epithelial dysfunction. An active infection of epithelial cells with RSV in vitro results in heightened central metabolism and overall hypermetabolic state; however, little is known about whether natural infection with RSV in vivo results in lasting metabolic reprogramming of the airway epithelium in infancy. To address this gap, we performed functional metabolomics, 13C glucose metabolic flux analysis, and RNA-seq gene expression analysis of nasal airway epithelial cells (NAECs) sampled from infants between 2–3 years of age, with RSV infection or not during the first year of life. We found that RSV infection in infancy was associated with lasting epithelial metabolic reprogramming, which was characterized by (1) significant increase in glucose uptake and differential utilization of glucose by epithelium; (2) altered preferences for metabolism of several carbon and energy sources; and (3) significant sexual dimorphism in metabolic parameters, with RSV-induced metabolic changes most pronounced in male epithelium. In summary, our study supports the proposed phenomenon of metabolic reprogramming of epithelial cells associated with RSV infection in infancy and opens exciting new venues for pursuing mechanisms of RSV-induced epithelial barrier dysfunction in early life. MDPI 2021-10-13 /pmc/articles/PMC8538412/ /pubmed/34696488 http://dx.doi.org/10.3390/v13102055 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Connelly, Andrew R. Jeong, Brian M. Coden, Mackenzie E. Cao, Jacob Y. Chirkova, Tatiana Rosas-Salazar, Christian Cephus, Jacqueline-Yvonne Anderson, Larry J. Newcomb, Dawn C. Hartert, Tina V. Berdnikovs, Sergejs Metabolic Reprogramming of Nasal Airway Epithelial Cells Following Infant Respiratory Syncytial Virus Infection |
title | Metabolic Reprogramming of Nasal Airway Epithelial Cells Following Infant Respiratory Syncytial Virus Infection |
title_full | Metabolic Reprogramming of Nasal Airway Epithelial Cells Following Infant Respiratory Syncytial Virus Infection |
title_fullStr | Metabolic Reprogramming of Nasal Airway Epithelial Cells Following Infant Respiratory Syncytial Virus Infection |
title_full_unstemmed | Metabolic Reprogramming of Nasal Airway Epithelial Cells Following Infant Respiratory Syncytial Virus Infection |
title_short | Metabolic Reprogramming of Nasal Airway Epithelial Cells Following Infant Respiratory Syncytial Virus Infection |
title_sort | metabolic reprogramming of nasal airway epithelial cells following infant respiratory syncytial virus infection |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538412/ https://www.ncbi.nlm.nih.gov/pubmed/34696488 http://dx.doi.org/10.3390/v13102055 |
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