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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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.
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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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