RNA Sequencing of H3N2 Influenza Virus-Infected Human Nasal Epithelial Cells from Multiple Subjects Reveals Molecular Pathways Associated with Tissue Injury and Complications
RNA Sequencing of H3N2 Influenza Virus-Infected Human Nasal Epithelial Cells from Multiple Subjects Reveals Molecular Pathways Associated with Tissue Injury and Complications
复制标题
对多个受试者感染 H3N2 流感病毒的人鼻上皮细胞进行 RNA 测序，揭示与组织损伤和并发症相关的分子通路
DOI：
10.3390/cells8090986
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发表时间：
2019-09-01
期刊：
影响因子：
6
通讯作者：
Wang, De Yun
中科院分区：
文献类型：
--
作者：
Tan, Kai Sen;Andiappan, Anand Kumar;Wang, De Yun
人鼻上皮是接触流感病毒的主要部位，是宿主对流感和由此产生的病理反应的始发者。流感病毒可能会引起严重的呼吸道感染，导致严重的并发症，以及严重的呼吸道损伤。在这里，我们阐明了H3N2感染多个个体的人鼻上皮细胞过程中的整体转录变化。使用RNA测序，我们描述了与感染后鼻黏膜上皮变化相关的差异表达基因和途径。我们使用了体外分化的人鼻上皮细胞培养模型，该模型来源于7个不同的捐赠者，这些捐赠者没有并发的病毒感染史。统计分析表明，强烈的转录信号与感染后24小时和48小时显著相关，但在较早的8小时时间点没有显著关联。特别是，我们发现流感感染早期就在鼻黏膜上皮细胞诱导，并改变了干扰素伽玛信号、B细胞信号、细胞凋亡、坏死、平滑肌增殖和代谢变化的反应。这些在受感染的鼻黏膜上皮细胞启动的分子事件可能会对呼吸道产生潜在的不利影响，因此我们确定的基因可能成为流感感染和相关疾病治疗的潜在诊断生物标志物或治疗靶点。
The human nasal epithelium is the primary site of exposure to influenza virus, the initiator of host responses to influenza and the resultant pathologies. Influenza virus may cause serious respiratory infection resulting in major complications, as well as severe impairment of the airways. Here, we elucidated the global transcriptomic changes during H3N2 infection of human nasal epithelial cells from multiple individuals. Using RNA sequencing, we characterized the differentially-expressed genes and pathways associated with changes occurring at the nasal epithelium following infection. We used in vitro differentiated human nasal epithelial cell culture model derived from seven different donors who had no concurrent history of viral infections. Statistical analysis highlighted strong transcriptomic signatures significantly associated with 24 and 48 h after infection, but not at the earlier 8-h time point. In particular, we found that the influenza infection induced in the nasal epithelium early and altered responses in interferon gamma signaling, B-cell signaling, apoptosis, necrosis, smooth muscle proliferation, and metabolic alterations. These molecular events initiated at the infected nasal epithelium may potentially adversely impact the airway, and thus the genes we identified could serve as potential diagnostic biomarkers or therapeutic targets for influenza infection and associated disease management.