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Whole blood gene expression in infants with respiratory syncytial virus bronchiolitis.

ABSTRACT: Respiratory syncytial virus (RSV) is a major cause of viral bronchiolitis in infants worldwide, and environmental, viral and host factors are all of importance for disease susceptibility and severity. To study the systemic host response to this disease we used the microarray technology to measure mRNA gene expression levels in whole blood of five male infants hospitalised with acute RSV, subtype B, bronchiolitis versus five one year old male controls exposed to RSV during infancy without bronchiolitis. The gene expression levels were further evaluated in a new experiment using quantitative real-time polymerase chain reaction (QRT-PCR) both in the five infants selected for microarray and in 13 other infants hospitalised with the same disease.Among the 30 genes most differentially expressed by microarray nearly 50% were involved in immunological processes. We found the highly upregulated interferon, alpha-inducible protein 27 (IFI27) and the highly downregulated gene Charcot-Leyden crystal protein (CLC) to be the two most differentially expressed genes in the microarray study. When performing QRT-PCR on these genes IFI27 was upregulated in all but one infant, and CLC was downregulated in all 18 infants, and similar to that given by microarray.The gene IFI27 is upregulated and the gene CLC is downregulated in whole blood of infants hospitalised with RSV, subtype B, bronchiolitis and is not reported before. More studies are needed to elucidate the specificity of these gene expressions in association with host response to this virus in bronchiolitis of moderate severity.

SUBMITTER: Fjaerli HO

PROVIDER: S-EPMC1713240 | biostudies-literature | 2006 Dec

REPOSITORIES: biostudies-literature

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Whole blood gene expression in infants with respiratory syncytial virus bronchiolitis.

Fjaerli Hans-Olav HO Bukholm Geir G Krog Anne A Skjaeret Camilla C Holden Marit M Nakstad Britt B

BMC infectious diseases 20061213

<h4>Background</h4>Respiratory syncytial virus (RSV) is a major cause of viral bronchiolitis in infants worldwide, and environmental, viral and host factors are all of importance for disease susceptibility and severity. To study the systemic host response to this disease we used the microarray technology to measure mRNA gene expression levels in whole blood of five male infants hospitalised with acute RSV, subtype B, bronchiolitis versus five one year old male controls exposed to RSV during infa ...[more]

PMID: 17166282

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Project description:BackgroundRespiratory syncytial virus (RSV) is the leading cause of viral lower respiratory tract infection (LRTI) and hospitalization in infants. Mostly because of the incomplete understanding of the disease pathogenesis, there is no licensed vaccine, and treatment remains symptomatic. We analyzed whole blood transcriptional profiles to characterize the global host immune response to acute RSV LRTI in infants, to characterize its specificity compared with influenza and human rhinovirus (HRV) LRTI, and to identify biomarkers that can objectively assess RSV disease severity.Methods and findingsThis was a prospective observational study over six respiratory seasons including a cohort of infants hospitalized with RSV (n?=?135), HRV (n?=?30), and influenza (n?=?16) LRTI, and healthy age- and sex-matched controls (n?=?39). A specific RSV transcriptional profile was identified in whole blood (training cohort, n?=?45 infants; Dallas, Texas, US) and validated in three different cohorts (test cohort, n?=?46, Dallas, Texas, US; validation cohort A, n?=?16, Turku, Finland; validation cohort B, n?=?28, Columbus, Ohio, US) with high sensitivity (94% [95% CI 87%-98%]) and specificity (98% [95% CI 88%-99%]). It classified infants with RSV LRTI versus HRV or influenza LRTI with 95% accuracy. The immune dysregulation induced by RSV (overexpression of neutrophil, inflammation, and interferon genes, and suppression of T and B cell genes) persisted beyond the acute disease, and immune dysregulation was greatly impaired in younger infants (<6 mo). We identified a genomic score that significantly correlated with outcomes of care including a clinical disease severity score and, more importantly, length of hospitalization and duration of supplemental O2.ConclusionsBlood RNA profiles of infants with RSV LRTI allow specific diagnosis, better understanding of disease pathogenesis, and assessment of disease severity. This study opens new avenues for biomarker discovery and identification of potential therapeutic or preventive targets, and demonstrates that large microarray datasets can be translated into a biologically meaningful context and applied to the clinical setting. Please see later in the article for the Editors' Summary.

Dataset Information

Whole blood gene expression in infants with respiratory syncytial virus bronchiolitis.

Publications

Whole blood gene expression in infants with respiratory syncytial virus bronchiolitis.

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