Reza Etemadi Mohammad, Ling King-Hwa, Zainal Abidin Shahidee, Chee Hui-Yee, Sekawi Zamberi
Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, University Putra Malaysia, UPM Serdang, Selangor DE, Malaysia.
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, UPM Serdang, Selangor DE, Serdang, Selangor, Malaysia.
PLoS One. 2017 May 30;12(5):e0176947. doi: 10.1371/journal.pone.0176947. eCollection 2017.
Human rhinovirus (HRV) is the common virus that causes acute respiratory infection (ARI) and is frequently associated with lower respiratory tract infections (LRTIs). We aimed to investigate whether HRV infection induces a specific gene expression pattern in airway epithelial cells. Alveolar epithelial cell monolayers were infected with HRV species B (HRV-B). RNA was extracted from both supernatants and infected monolayer cells at 6, 12, 24 and 48 hours post infection (hpi) and transcriptional profile was analyzed using Affymetrix GeneChip and the results were subsequently validated using quantitative Real-time PCR method. HRV-B infects alveolar epithelial cells which supports implication of the virus with LRTIs. In total 991 genes were found differentially expressed during the course of infection. Of these, 459 genes were up-regulated whereas 532 genes were down-regulated. Differential gene expression at 6 hpi (187 genes up-regulated vs. 156 down-regulated) were significantly represented by gene ontologies related to the chemokines and inflammatory molecules indicating characteristic of viral infection. The 75 up-regulated genes surpassed the down-regulated genes (35) at 12 hpi and their enriched ontologies fell into discrete functional entities such as regulation of apoptosis, anti-apoptosis, and wound healing. At later time points of 24 and 48 hpi, predominated down-regulated genes were enriched for extracellular matrix proteins and airway remodeling events. Our data provides a comprehensive image of host response to HRV infection. The study suggests the underlying molecular regulatory networks genes which might be involved in pathogenicity of the HRV-B and potential targets for further validations and development of effective treatment.
人鼻病毒(HRV)是引起急性呼吸道感染(ARI)的常见病毒,且常与下呼吸道感染(LRTIs)相关。我们旨在研究HRV感染是否会在气道上皮细胞中诱导特定的基因表达模式。用B型人鼻病毒(HRV-B)感染肺泡上皮细胞单层。在感染后6、12、24和48小时(hpi)从上清液和感染的单层细胞中提取RNA,并使用Affymetrix基因芯片分析转录谱,随后使用定量实时PCR方法验证结果。HRV-B感染肺泡上皮细胞,这支持了该病毒与下呼吸道感染的关联。在感染过程中总共发现991个基因差异表达。其中,459个基因上调,而532个基因下调。在6 hpi时差异基因表达(187个基因上调对156个基因下调)由与趋化因子和炎症分子相关的基因本体显著代表,表明病毒感染的特征。在12 hpi时,75个上调基因超过了下调基因(35个),它们富集的本体落入离散的功能实体,如细胞凋亡调节、抗凋亡和伤口愈合。在24和48 hpi的后期时间点,下调基因主要富集于细胞外基质蛋白和气道重塑事件。我们的数据提供了宿主对HRV感染反应的全面图景。该研究揭示了可能参与HRV-B致病性的潜在分子调控网络基因以及进一步验证和开发有效治疗方法的潜在靶点。