Identification of gene biomarkers for respiratory syncytial virus infection in a bronchial epithelial cell line

Abstract
Respiratory syncytial virus (RSV) infection involves complex virus-host interplay. In this study, we analyzed gene expression in RSV-infected BEAS-2B cells to discover novel signaling pathways and biomarkers. We hybridized RNAs from RSV- or vehicle-treated BEAS-2B to Affymetrix HU133 plus 2.0 microarrays (n = 4). At 4 and 24 h post-infection, 277 and 900 genes (RSV/control ratio ≥2.0 or ≤0.5), and 1 and 12 pathways respectively were significantly altered. Twenty-three and 92 genes at 4 and 24 h respectively matched respiratory disease biomarkers with ARG2 flagged at 24 h and SCNN1G, EPB41L4B, CSF1, PTEN, TUBB1 and ESR2 at both time points. Hierachical clustering showed a cluster containing ARG2 and IL8. In human bronchial epithelial cells, RSV upregulated arginase II protein. Knockdown of ARG2 increased RSV-induced IL-8, LDH and histone release. With microarray, we identified novel proximal airway epithelial cell genes that may be tested in the sputum samples as biomarkers of RSV infection.