Background Preterm infants are a special population that vulnerable to respiratory syncytial virus (RSV) infection and the lower respiratory tract infections (LRTIs) caused by RSV could be severe and even life-threating. The purpose of the present study was to identify candidate genes of preterm infants who are susceptible to RSV infection and provide a new insight into the pathogenesis of RSV infection. Methods Three datasets (GSE77087, GSE69606 and GSE41374) containing 183 blood samples of RSV infected patients and 33 blood samples of healthy controls from Gene Expression Omnibus (GEO) database were downloaded and the differentially expressed genes (DEGs) were screened out. The function and pathway enrichments were analyzed through Database for Annotation, Visualization and Integrated Discovery (DAVID) website. The protein-protein interaction (PPI) network for DEGs was constructed through Search Tool for the Retrieval of Interacting Genes (STRING). The module analysis was performed by Cytoscape software and hub genes were identified. Clinical verification was employed to verify the expression level of top five hub genes among 72 infants including 50 RSV infected patients and 22 non-RSV-infected patients hospitalized in our center. Further, the RSV infected infants with high-expression IFI27 and those with low-expression IFI27 were compared (defined as higher or lower than the median mRNA level). Finally, the gene set enrichment analysis (GSEA) focusing on IFI27 was carried out. Results Totally, 4028 DEGs were screened out and among which, 131 most significant DEGs were selected. Subsequently, 13 hub genes were identified, and function and pathway enrichments of hub genes mainly were: response to virus, defense response to virus, regulation of viral genome replication and regulation of viral life cycle. Furthermore, IFI27 was confirmed to be the most significantly expressed in clinical verification. Gene sets associated with calcium signaling pathway, arachidonic acid metabolism, extracellular matrix receptor interaction and so on were significantly enriched when IFI27 was highly expressed. Moreover, high-expression IFI27 was associated with more severe cases ( p = 0.041), more requirements of mechanical ventilation ( p = 0.034), more frequent hospitalization ( p < 0.001) and longer cumulative hospital stay ( p = 0.012). Conclusion IFI27 might serve to predict RSV infection and evaluate the severity of RSV infection in preterm infants.

中文翻译：

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IFI27 可预测和评估早产儿呼吸道合胞病毒感染的严重程度

背景早产儿是一个特殊的人群，容易受到呼吸道合胞病毒（RSV）感染，由RSV引起的下呼吸道感染（LRTIs）可能很严重，甚至危及生命。本研究的目的是确定易受 RSV 感染的早产儿的候选基因，并为 RSV 感染的发病机制提供新的见解。方法 下载基因表达综合（GEO）数据库中包含183份RSV感染患者血样和33份健康对照血样的数据集（GSE77087、GSE69606和GSE41374），筛选出差异表达基因（DEGs）。通过注释、可视化和集成发现数据库 (DAVID) 网站分析了功能和通路富集。DEG 的蛋白质-蛋白质相互作用 (PPI) 网络是通过用于检索相互作用基因的搜索工具 (STRING) 构建的。通过Cytoscape软件进行模块分析并鉴定hub基因。采用临床验证方法，对我中心住院的72例婴儿RSV感染者50例和非RSV感染者22例中前5位hub基因的表达水平进行验证。此外，还比较了感染了高表达 IFI27 的 RSV 婴儿和低表达 IFI27 的婴儿（定义为高于或低于中位 mRNA 水平）。最后，进行了以 IFI27 为重点的基因集富集分析（GSEA）。结果共筛选出4028个DEG，从中选出最显着的131个DEG。随后，确定了13个枢纽基因，枢纽基因的功能和通路富集主要有：对病毒的反应、对病毒的防御反应、病毒基因组复制的调控和病毒生命周期的调控。此外，IFI27被证实在临床验证中表达最显着。当IFI27高表达时，与钙信号通路、花生四烯酸代谢、细胞外基质受体相互作用等相关的基因组显着丰富。此外，高表达 IFI27 与更严重的病例 (p = 0.041)、更多的机械通气需求 (p = 0.034)、更频繁的住院 (p < 0.001) 和更长的累积住院时间 (p = 0.012) 相关。结论 IFI27可用于预测RSV感染并评估早产儿RSV感染的严重程度。