Using urine metabolomics to understand the pathogenesis of infant respiratory syncytial virus (RSV) infection and its role in childhood wheezing

• Type of Material: Article
• Authors: Kedir N. Turi, Vanderbilt University; Lindsey Romick-Rosendale, University of Cincinnati; Tebeb Gebretsadik, Vanderbilt University; Miki Watanabe, University of Cincinnati; Steven Brunwasser, Vanderbilt University; Larry Anderson, Emory University; Martin Moore, Emory University; Emma K. Larkin, Vanderbilt University; Ray Stokes Peebles, Vanderbilt University; Tina Hartert, Vanderbilt University
• Language: English
• Date: 2018-10-01
• Publisher: Springer Verlag (Germany)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018, Springer Science+Business Media, LLC, part of Springer Nature.
• Final Published Version (URL): http://dx.doi.org/10.1007/s11306-018-1431-z
• Title of Journal or Parent Work: Metabolomics
• ISSN: 1573-3882
• Volume: 14
• Issue: 10
• Start Page: 135
• End Page: 135
• Grant/Funding Information: The funding was provided by National Institute of Allergy and Infectious Diseases.; This work was supported by the National Institute of Health U19AI95227, K24 AI 77930, R21HD087864, and T32HL087738.
• Keywords: BRONCHIOLITIS; METABOLISM; Urine metabolomics; BETAINE; EARLY-LIFE; Infant; TRACT INFECTIONS; Life Sciences & Biomedicine; Science & Technology; Endocrinology & Metabolism; HUMAN CYTOMEGALOVIRUS-INFECTION; VALIDATION; DNA METHYLATION; FOLATE; Recurrent wheezing; ASTHMA; Respiratory syncytial virus
• Research Categories: Health Sciences, Pathology; Biology, Virology; Health Sciences, Medicine and Surgery

Abstract

Background: Respiratory syncytial virus (RSV) infection in infants causes significant morbidity and is the strongest risk factor associated with asthma. Metabolites, which reflect the interactions between host cell and virus, provide an opportunity to identify the pathways that underlie severe infections and asthma development. Objective: To study metabolic profile differences between infants with RSV infection, and human rhinovirus (HRV) infection, and healthy infants. To compare infant metabolic differences between children who do and do not wheeze. Methods: In a term birth cohort, urine was collected while healthy and during acute viral respiratory infection with RSV and HRV. We used 1 H-NMR to identify urinary metabolites. Multivariate and univariate statistics were used to discriminate metabolic profiles of infants with either RSV ARI, or HRV ARI, and healthy infants. Multivariable logistic regression was used to assess the association of urine metabolites with 1st-, 2nd-, and 3rd-year recurrent wheezing. Results: Several metabolites in nicotinate and nicotinamide metabolism pathways were down-regulated in infants with RSV infection compared to healthy controls. There were no significant differences in metabolite profiles between infants with RSV infection and infants with HRV Infection. Alanine was strongly associated with reduced risk of 1st-year wheezing (OR 0.18[0.0, 0.46]) and 2nd-year wheezing (OR 0.31[0.13, 0.73]), while 2-hydroxyisobutyric acid was associated with increased 3rd-year wheezing (OR 5.02[1.49, 16.93]) only among the RSV infected subset. Conclusion: The metabolites associated with infant RSV infection and recurrent-wheezing are indicative of viral takeover of the cellular machinery and resources to enhance virulence, replication, and subversion of the host immune-response, highlighting metabolic pathways important in the pathogenesis of RSV infection and wheeze development.