Meng Jun, Yao Zhenyu, He Yaqing, Zhang Renli, Yang Hong, Yao Xiangjie, Chen Long, Zhang Hailong, Cheng Jinquan
Shenzhen Center for Disease Control and Prevention, Shenzhen, Guangdong, China.
Department of Translational Medicine R&D Center, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China.
Biochem Biophys Res Commun. 2017 Dec 2;493(4):1594-1600. doi: 10.1016/j.bbrc.2017.09.141. Epub 2017 Oct 7.
Enterovirus 71 (EV71) is associated with the severe hand foot and mouth disease (HFMD) outcomes, however the host-virus interaction mechanism and the pathogenesis remain poorly understood. Long non-coding RNAs (lncRNAs) are involved in variety physiological and pathological processes, but the functions of lncRNAs in EV71 infection remain elusive. Here we profiled the expression of lncRNAs in peripheral blood mononuclear cells (PBMCs) from EV71-infected mild patients, severe patients as well as the healthy controls, and identified 8541 lncRNAs were differentially expressed. Focused on the dynamic changed lncRNAs, we performed systematic bioinformatics analysis with Series Test of Cluster (STC) algorithm, Gene Ontology (GO) analysis, pathway analysis and lncRNA-mRNA co-expression network analysis, and revealed the potential functions and related pathways of these lncRNAs were associated with immunity and inflammation during the clinical process of EV71-infected HFMD. Among the significant dynamic changed lncRNAs, ten lncRNAs were screened whose expression were further validated in EV71-infected mild patients, severe patients and healthy control. These results shed light on the potential roles of lncRNAs in EV71-infected HFMD, especially in distinguishing the mild and severe cases for early diagnose and treatment, moreover, provide deeper insight into the mechanism of EV71-induced immune and inflammatory responses, as well as the pathogenesis of the imbalanced inflammation in severe EV71 infection.
肠道病毒71型（EV71）与严重手足口病（HFMD）的发病结果相关，然而宿主与病毒的相互作用机制及发病机制仍知之甚少。长链非编码RNA（lncRNAs）参与多种生理和病理过程，但lncRNAs在EV71感染中的功能仍不清楚。在此，我们分析了EV71感染的轻症患者、重症患者以及健康对照外周血单个核细胞（PBMCs）中lncRNAs的表达情况，鉴定出8541个lncRNAs存在差异表达。聚焦于动态变化的lncRNAs，我们运用聚类序列检验（STC）算法、基因本体（GO）分析、通路分析和lncRNA-mRNA共表达网络分析进行了系统的生物信息学分析，揭示了这些lncRNAs在EV71感染的手足口病临床过程中潜在的功能及相关通路与免疫和炎症相关。在显著动态变化的lncRNAs中，筛选出10个lncRNAs，其表达在EV71感染的轻症患者、重症患者及健康对照中进一步得到验证。这些结果揭示了lncRNAs在EV71感染的手足口病中的潜在作用，特别是在区分轻症和重症病例以进行早期诊断和治疗方面，此外，还为深入了解EV71诱导的免疫和炎症反应机制以及重症EV71感染中炎症失衡的发病机制提供了依据。
