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全面的生物信息学分析树突状细胞对抗麻疹病毒的免疫机制。

Comprehensive Bioinformatics Analysis of the Immune Mechanism of Dendritic Cells Against Measles Virus.

机构信息

College of Humanities and Management, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, China (mainland).

College of Public Health, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, China (mainland).

出版信息

Med Sci Monit. 2019 Feb 1;25:903-912. doi: 10.12659/MSM.912949.

DOI:10.12659/MSM.912949
PMID:30705250
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6367888/
Abstract

BACKGROUND The purpose of this study was to explore the immune mechanism of dendritic cells (DCs) against measles virus (MV), and to identify potential biomarkers to improve measles prevention and treatment. MATERIAL AND METHODS The gene expression profile of GSE980, which comprised 10 DC samples from human blood infected with MV (RNA was isolated at 3, 6, 12, and 24 h post-infection) and 4 normal DC control samples, was obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between the MV-infected DC samples and the control samples were screened using Genevestigator software. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were performed using GenCLip 2.0 and STRING 10.5 software. The protein-protein interaction (PPI) network was established using Cytoscape 3.4.0. RESULTS The gene expression profiles of MV-infected DCs were obviously changed. Twenty-six common DEGs (0.9%, MV-infected DCs vs. normal DCs) were identified at 4 different time points, including 14 down-regulated and 12 up-regulated genes (P=0.001). GO analysis showed that DEGs were significantly enriched in defense response to virus, type I interferon signaling pathway, et al. ISG15 and CXCL10 were the key genes in the PPI network of the DEGs, and may interact directly with the type I interferon signaling and defense response to virus signaling. CONCLUSIONS The DEGs increased gradually with the duration of MV infection. The type I interferon signaling pathway and the defense response to viral processes can be activated against MV by ISG15 and CXCL10 in DCs. These may provide novel targets for the treatment of MV.

摘要

背景

本研究旨在探讨树突状细胞(DCs)对麻疹病毒(MV)的免疫机制,寻找潜在的生物标志物,以提高麻疹的预防和治疗水平。

材料和方法

从基因表达综合数据库中获取 GSE980 数据集,该数据集包含 10 个人血源性树突状细胞样本,这些样本在感染 MV 后(分别在感染后 3、6、12 和 24 小时提取 RNA)和 4 个正常树突状细胞对照样本,采用 Genevestigator 软件筛选 MV 感染的 DC 样本与对照样本之间的差异表达基因(DEGs)。使用 GenCLip 2.0 和 STRING 10.5 软件进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路富集分析。使用 Cytoscape 3.4.0 构建蛋白质-蛋白质相互作用(PPI)网络。

结果

MV 感染的 DC 基因表达谱明显改变。在 4 个不同时间点共鉴定出 26 个常见的 DEGs(0.9%,MV 感染的 DC 与正常 DC 相比),包括 14 个下调基因和 12 个上调基因(P=0.001)。GO 分析表明,DEGs 显著富集于抗病毒防御反应、I 型干扰素信号通路等通路。ISG15 和 CXCL10 是 DEGs PPI 网络中的关键基因,可能与 I 型干扰素信号和抗病毒防御反应信号直接相互作用。

结论

随着 MV 感染时间的延长,DEGs 逐渐增加。ISG15 和 CXCL10 可激活 DC 中的 I 型干扰素信号通路和抗病毒防御反应过程,从而对 MV 产生免疫反应。这些发现可能为 MV 的治疗提供新的靶点。

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