Respiratory Syncytial Virus Elicits Glycolytic Metabolism in Pediatric Upper and Lower Airways
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract viral infection in infants and causes around 60,000 in-hospital deaths annually. Emerging evidence suggests that RSV induces metabolic changes in host cells to support viral replication, presenting a potential target f...
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| Format: | Article |
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MDPI AG
2025-05-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/17/5/703 |
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| author | Armando S. Flores-Torres Svetlana Rezinciuc Lavanya Bezavada Barry L. Shulkin Stephania A. Cormier Heather S. Smallwood |
| author_facet | Armando S. Flores-Torres Svetlana Rezinciuc Lavanya Bezavada Barry L. Shulkin Stephania A. Cormier Heather S. Smallwood |
| author_sort | Armando S. Flores-Torres |
| collection | DOAJ |
| description | Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract viral infection in infants and causes around 60,000 in-hospital deaths annually. Emerging evidence suggests that RSV induces metabolic changes in host cells to support viral replication, presenting a potential target for therapeutic intervention. To investigate RSV-driven metabolic changes in situ, we combined positron emission tomography (PET), live-cell bioenergetics, and metabolomic profiling in the upper and lower airways of children. PET imaging revealed persistent, hyper-glycolytic regions in the lungs of RSV-infected children. Bioenergetic analysis of freshly collected nasopharyngeal aspirates from infants showed live upper respiratory cells (URCs) infected with RSV in situ exhibited significantly higher levels of glycolysis, glycolytic capacity, glycolytic reserves, and mitochondrial respiration than uninfected controls. Metabolomic analysis of nasopharyngeal fluids from these patients revealed distinct metabolic signatures, including increased citrate and malate, and decreases in taurine. In vitro infection of pediatric nasopharynx tissue-derived multicellular epithelial cultures (TEpiCs) and bronchial epithelial cells further confirmed RSV-induced increases in glycolysis. Together, these findings demonstrate that RSV infection induces hypermetabolism in both upper and lower primary airways in situ, supporting the potential of host-targeted metabolic interventions as a therapeutic strategy—particularly in vulnerable populations such as infants for whom vaccines are not currently available. |
| format | Article |
| id | doaj-art-30a62c63d015408eb293cdacff05de3e |
| institution | DOAJ |
| issn | 1999-4915 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj-art-30a62c63d015408eb293cdacff05de3e2025-08-20T03:12:09ZengMDPI AGViruses1999-49152025-05-0117570310.3390/v17050703Respiratory Syncytial Virus Elicits Glycolytic Metabolism in Pediatric Upper and Lower AirwaysArmando S. Flores-Torres0Svetlana Rezinciuc1Lavanya Bezavada2Barry L. Shulkin3Stephania A. Cormier4Heather S. Smallwood5Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38103, USADepartment of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38103, USADepartment of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38103, USADepartment of Biological Sciences, Louisiana State University, Pennington Biomedical Research Center, Baton Rouge, LA 70803, USADepartment of Diagnostic Imaging, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38103, USARespiratory syncytial virus (RSV) is the leading cause of lower respiratory tract viral infection in infants and causes around 60,000 in-hospital deaths annually. Emerging evidence suggests that RSV induces metabolic changes in host cells to support viral replication, presenting a potential target for therapeutic intervention. To investigate RSV-driven metabolic changes in situ, we combined positron emission tomography (PET), live-cell bioenergetics, and metabolomic profiling in the upper and lower airways of children. PET imaging revealed persistent, hyper-glycolytic regions in the lungs of RSV-infected children. Bioenergetic analysis of freshly collected nasopharyngeal aspirates from infants showed live upper respiratory cells (URCs) infected with RSV in situ exhibited significantly higher levels of glycolysis, glycolytic capacity, glycolytic reserves, and mitochondrial respiration than uninfected controls. Metabolomic analysis of nasopharyngeal fluids from these patients revealed distinct metabolic signatures, including increased citrate and malate, and decreases in taurine. In vitro infection of pediatric nasopharynx tissue-derived multicellular epithelial cultures (TEpiCs) and bronchial epithelial cells further confirmed RSV-induced increases in glycolysis. Together, these findings demonstrate that RSV infection induces hypermetabolism in both upper and lower primary airways in situ, supporting the potential of host-targeted metabolic interventions as a therapeutic strategy—particularly in vulnerable populations such as infants for whom vaccines are not currently available.https://www.mdpi.com/1999-4915/17/5/703RSVrespiratory syncytial virusmetabolismairway epithelial cellspediatricglycolysis |
| spellingShingle | Armando S. Flores-Torres Svetlana Rezinciuc Lavanya Bezavada Barry L. Shulkin Stephania A. Cormier Heather S. Smallwood Respiratory Syncytial Virus Elicits Glycolytic Metabolism in Pediatric Upper and Lower Airways Viruses RSV respiratory syncytial virus metabolism airway epithelial cells pediatric glycolysis |
| title | Respiratory Syncytial Virus Elicits Glycolytic Metabolism in Pediatric Upper and Lower Airways |
| title_full | Respiratory Syncytial Virus Elicits Glycolytic Metabolism in Pediatric Upper and Lower Airways |
| title_fullStr | Respiratory Syncytial Virus Elicits Glycolytic Metabolism in Pediatric Upper and Lower Airways |
| title_full_unstemmed | Respiratory Syncytial Virus Elicits Glycolytic Metabolism in Pediatric Upper and Lower Airways |
| title_short | Respiratory Syncytial Virus Elicits Glycolytic Metabolism in Pediatric Upper and Lower Airways |
| title_sort | respiratory syncytial virus elicits glycolytic metabolism in pediatric upper and lower airways |
| topic | RSV respiratory syncytial virus metabolism airway epithelial cells pediatric glycolysis |
| url | https://www.mdpi.com/1999-4915/17/5/703 |
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