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Title: Global gene expression profiling in infants with acute respiratory syncytial virus broncholitis demonstrates systemic activation of interferon signaling networks

Author
item Bucasas, Kristine - Baylor College Of Medicine
item Mian, Asad - Baylor College Of Medicine
item Demmler-harrison, Gail - Baylor College Of Medicine
item Caviness, Alison - Baylor College Of Medicine
item Piedra, Pedro - Baylor College Of Medicine
item Franco, Luis - Baylor College Of Medicine
item Shaw, Chad - Baylor College Of Medicine
item Zhai, Yijie - Baylor College Of Medicine
item Wang, Xueqing - Baylor College Of Medicine
item Bray, Molly - University Of Alabama
item Couch, Robert - Baylor College Of Medicine
item Belmont, John - Children'S Nutrition Research Center (CNRC)

Submitted to: The Pediatric Infectious Disease Journal
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/20/2012
Publication Date: 2/1/2013
Citation: Bucasas, K.L., Mian, A.I., Demmler-Harrison, G.J., Caviness, A.C., Piedra, P.A., Franco, L.M., Shaw, C.A., Zhai, Y., Wang, X., Bray, M.S., Couch, R.B., Belmont, J.W. 2013. Global gene expression profiling in infants with acute respiratory syncytial virus broncholitis demonstrates systemic activation of interferon signaling networks. The Pediatric Infectious Disease Journal. 32(2):E68-E76.

Interpretive Summary: Respiratory syncytial virus (RSV) is a leading cause of pediatric pneumonia and affects children with either micronutrient or macronutrient nutritional deficiencies. We studied infants with acute RSV infection compared to normal controls using gene expression. Using microarray technology, we found a consistent signature of acute infection that was present in infants with both mild and moderate disease. For the first time we demonstrated that the virus induces a kind of immune paralysis in which the ability of the cellular immune system to respond is shut down. The data from this study also identified numerous genes involved in how the body makes and uses energy that must respond during the viral infection. These results help us to understand how nutritional deficiencies lead to an increased risk of severe complications in RSV infection.

Technical Abstract: Respiratory syncytial virus (RSV) is a leading cause of pediatric lower respiratory tract infections and has a high impact on pediatric emergency department utilization. Variation in host response may influence the pathogenesis and disease severity. We evaluated global gene expression profiles to better understand the systemic host response to acute RSV bronchiolitis in infants and young children. Patients (age = 24 months) who were clinically diagnosed with acute bronchiolitis and who had a positive rapid test for RSV assay were recruited from the Texas Children's Hospital emergency department. Global gene expression of peripheral whole blood cells were analyzed in 21 cases and 37 age-matched healthy controls. Transcripts exhibiting significant upregulation and downregulation as a result of RSV infection were identified and confirmed in a subset of samples using RNA sequencing. The potential pathways affected were analyzed. Blood was obtained from patients with acute RSV bronchiolitis (mean age 6 months). Of these, 43% were admitted to the hospital, 52% were given intravenous fluids, and 24% received oxygen. Highly significant expression differences were detected in a discovery cohort of White infants (N = 33) and validated in an independent group of African-American infants (N = 19). Individuals with mild disease (N = 15) could not be distinguished from subjects with clinically moderate disease (N = 5). Pathway enrichment analyses of the differentially expressed genes demonstrated extensive activation of the innate immune response, particularly the interferon signaling network. There was a significant downregulation of transcripts corresponding to antigen presentation.