{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:17:10Z","timestamp":1791472630393,"version":"4.3.4"},"reference-count":39,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T00:00:00Z","timestamp":1634083200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U19 AI095227"],"award-info":[{"award-number":["U19 AI095227"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UL1TR000445"],"award-info":[{"award-number":["UL1TR000445"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI127783"],"award-info":[{"award-number":["R01AI127783"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>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\u20133 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.<\/jats:p>","DOI":"10.3390\/v13102055","type":"journal-article","created":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T21:55:02Z","timestamp":1634162102000},"page":"2055","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Metabolic Reprogramming of Nasal Airway Epithelial Cells Following Infant Respiratory Syncytial Virus Infection"],"prefix":"10.3390","volume":"13","author":[{"given":"Andrew R.","family":"Connelly","sequence":"first","affiliation":[{"name":"Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian M.","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mackenzie E.","family":"Coden","sequence":"additional","affiliation":[{"name":"Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3624-7489","authenticated-orcid":false,"given":"Jacob Y.","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Chirkova","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine and Children\u2019s Healthcare of Atlanta, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Rosas-Salazar","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline-Yvonne","family":"Cephus","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry J.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine and Children\u2019s Healthcare of Atlanta, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn C.","family":"Newcomb","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA"},{"name":"Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina V.","family":"Hartert","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37203, USA"},{"name":"Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergejs","family":"Berdnikovs","sequence":"additional","affiliation":[{"name":"Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e1031","DOI":"10.1016\/S2214-109X(19)30264-5","article-title":"Global patterns in monthly activity of influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus: A systematic analysis","volume":"7","author":"Li","year":"2019","journal-title":"Lancet Glob. 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