Comparison analysis of microRNAs in response to EV71 and CA16 infection in human bronchial epithelial cells by high-throughput sequencing to reveal differential infective mechanisms
Comparison analysis of microRNAs in response to EV71 and CA16 infection in human bronchial epithelial cells by high-throughput sequencing to reveal differential infective mechanisms
复制标题
通过高通量测序比较分析人支气管上皮细胞中 EV71 和 CA16 感染的 microRNA，揭示不同的感染机制
DOI：
10.1016/j.virusres.2016.11.024
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发表时间：
2017-01-15
期刊：
影响因子：
5
通讯作者：
Li, Qihan
中科院分区：
文献类型：
--
作者：
Hu, Yajie;Song, Jie;Li, Qihan
手足口病（HFMD）主要由肠道病毒71型（EV 71）和柯萨奇病毒A16型（CA 16）感染引起，两种病毒感染的临床表现差异显著。然而，这些差异背后的因素仍不清楚。近年来，microRNAs（miRNAs）在病原体-宿主相互作用中的作用受到了广泛关注。在这里，我们在EV 71和CA 16感染的人支气管上皮（16 HBE）细胞中进行了全面的miRNA分析，在多个时间点使用高通量测序。结果显示，154个已知的miRNAs和47个新发现的miRNAs的表达存在显著差异。其中，65种miRNAs，包括58种已知的和7种新的miRNAs，在EV 71和CA 16感染的样品中呈现相反的趋势。随后，我们主要对已知的56个差异表达的miRNAs进行进一步筛选，进行靶点预测。对这些靶点的GO和通路分析表明，富集了18个生物学过程、7个分子功能、1个细胞组分和123条通路。其中钙粘蛋白信号通路、Wnt信号通路和血管生成发生了显著改变。这些miRNAs的调控网络具有预测的靶点、靶点、通路和转录因子，表明miRNAs在感染阶段表现出复杂的调控机制。因此，我们专门分析了参与粘附的预测靶点的分级GO类别。结果提示，EV 71和CA 16感染引起的气道上皮屏障功能的明显改变可能与气道上皮屏障功能的改变有关。总之，我们的数据提供了有用的见解，有助于阐明EV 71和CA 16感染后不同的宿主-病原体相互作用，并可能为这些感染提供新的治疗靶点。(C)2016年6月，作者。由爱思唯尔公司出版。这是一篇开放获取的文章，获得了CC BY-NC-ND许可证（http：//creativecommons.org/licenses/by-nc-nd/4.0/）。
Hand, foot, and mouth disease (HFMD) mainly caused by Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) infections which presented significantly different clinical manifestations. Nevertheless, the factors underlying these differences remain unclear. Recently, the functions of microRNAs (miRNAs) in pathogen-host interactions have been highlighted. Here, we performed comprehensive miRNA profiling in EV71- and CA16-infected human bronchial epithelial (16HBE) cells at multiple time points using high throughput sequencing. The results showed that 154 known and 47 novel miRNAs exhibited remarkable differences in expression. Of these, 65 miRNAs, including 58 known and 7 novel miRNAs, presented opposite trends in EV71- and CA16-infected samples. Subsequently, we mainly focused on the 56 known differentially expressed miRNAs by further screening for targets prediction. GO and pathway analysis of these targets demonstrated that 18 biological processes, 7 molecular functions, 1 cellular component and 123 pathways were enriched. Among these pathways, Cadherin signalling pathway, Wnt signalling pathway and angiogenesis showed significant alterations. The regulatory networks of these miRNAs with predicted targets, GOs, pathways and transcription factors were determined, which suggested that miRNAs displayed intricate regulatory mechanisms during the infection phase. Consequently, we specifically analysed the hierarchical GO categories of the predicted targets involved in adhesion. The results indicated that the distinct changes induced by EV71 and CA16 infection may be partly linked to airway epithelial barrier function. Taken together, our data provide useful insights that help elucidate the different host-pathogen interactions following EV71 and CA16 infection and might offer novel therapeutic targets for these infections. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).