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

Kristine L. Bucasas, Asad I. Mian, Gail J. Demmler-Harrison, Alison C. Caviness, Pedro A. Piedra, Luis M. Franco, Chad A. Shaw, Yijie Zhai, Xueqing Wang, Molly S. Bray, Robert B. Couch, John W. Belmont

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

BACKGROUND: 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. METHODS: 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. RESULTS: 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.

Original languageEnglish
Pages (from-to)e68-e76
JournalPediatric Infectious Disease Journal
Volume32
Issue number2
DOIs
Publication statusPublished - Feb 2013
Externally publishedYes

Keywords

  • gene expression profile
  • infant
  • respiratory syncytial virus

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