Huang Yuh-Chin T, Li Zhuowei, Hyseni Xhevahire, Schmitt Michael, Devlin Robert B, Karoly Edward D, Soukup Joleen M
Department of Medicine, Duke University Medical Center, Box 2733, Durham, NC, 27710, USA,
Genomic Med. 2008 Dec;2(3-4):113-25. doi: 10.1007/s11568-009-9080-y. Epub 2009 May 15.
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.
呼吸道合胞病毒(RSV)感染涉及复杂的病毒-宿主相互作用。在本研究中,我们分析了RSV感染的BEAS-2B细胞中的基因表达,以发现新的信号通路和生物标志物。我们将来自RSV处理或未处理的BEAS-2B细胞的RNA与Affymetrix HU133 plus 2.0微阵列(n = 4)进行杂交。在感染后4小时和24小时,分别有277个和900个基因(RSV/对照比值≥2.0或≤0.5)以及1条和12条信号通路发生显著改变。在4小时和24小时分别有23个和92个基因与呼吸道疾病生物标志物匹配,其中24小时时为精氨酸酶2(ARG2),两个时间点均为SCNN1G、EPB41L4B、集落刺激因子1(CSF1)、第10号染色体缺失的磷酸酶及张力蛋白同源物(PTEN)、微管蛋白β1(TUBB1)和雌激素受体2(ESR2)。层次聚类显示一个包含ARG2和白细胞介素8(IL-8)的簇。在人支气管上皮细胞中,RSV上调了精氨酸酶II蛋白。敲低ARG2会增加RSV诱导的IL-8、乳酸脱氢酶(LDH)和组蛋白释放。通过微阵列,我们鉴定了可能在痰液样本中作为RSV感染生物标志物进行检测的新的近端气道上皮细胞基因。