Metabolic Reprogramming of Nasal Airway Epithelial Cells Following Infant Respiratory Syncytial Virus Infection
| Autor: | Christian Rosas-Salazar, Brian M. Jeong, Dawn C. Newcomb, Tina V. Hartert, Jacqueline Cephus, Andrew R. Connelly, Larry J. Anderson, Tatiana Chirkova, Jacob Y. Cao, Mackenzie E. Coden, Sergejs Berdnikovs |
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| Rok vydání: | 2021 |
| Předmět: |
Male
viruses respiratory syncytial virus Glucose uptake Respiratory Mucosa Respiratory Syncytial Virus Infections Microbiology Article Virus Cohort Studies Virology medicine Humans Metabolomics glucose Respiratory system Respiratory Tract Infections Pathogen business.industry Infant Newborn Infant Respiratory infection Epithelial Cells respiratory system QR1-502 Epithelium Respiratory Syncytial Viruses Infectious Diseases medicine.anatomical_structure Child Preschool Immunology Respiratory epithelium Female Nasal Cavity airway epithelial cells Energy source business metabolism |
| Zdroj: | Viruses Volume 13 Issue 10 Viruses, Vol 13, Iss 2055, p 2055 (2021) |
| ISSN: | 1999-4915 |
| DOI: | 10.3390/v13102055 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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