细胞对人巨细胞病毒感染的反应：诱导间充质到上皮的转变（MET）表型。
Cellular responses to human cytomegalovirus infection: Induction of a mesenchymal-to-epithelial transition (MET) phenotype.
机构信息
Department of Molecular Biology, Princeton University, Princeton, NJ 08544.
Department of Molecular Biology, Princeton University, Princeton, NJ 08544
出版信息
Proc Natl Acad Sci U S A. 2017 Sep 26;114(39):E8244-E8253. doi: 10.1073/pnas.1710799114. Epub 2017 Sep 5.
Abstract
Human cytomegalovirus (HCMV) is the prototypical human β-herpes virus. Here we perform a systems analysis of the HCMV host-cell transcriptome, using gene set enrichment analysis (GSEA) as an engine to globally map the host-pathogen interaction across two cell types. Our analysis identified several previously unknown signatures of infection, such as induction of potassium channels and amino acid transporters, derepression of genes marked with histone H3 lysine 27 trimethylation (H3K27me3), and inhibition of genes related to epithelial-to-mesenchymal transition (EMT). The repression of EMT genes was dependent on early viral gene expression and correlated with induction E-cadherin (CDH1) and mesenchymal-to-epithelial transition (MET) genes. Infection of transformed breast carcinoma and glioma stem cells similarly inhibited EMT and induced MET, arguing that HCMV induces an epithelium-like cellular environment during infection.
摘要
人类巨细胞病毒（HCMV）是典型的人类β疱疹病毒。在这里，我们使用基因集富集分析（GSEA）作为引擎，对 HCMV 宿主细胞转录组进行系统分析，以全局绘制两种细胞类型中宿主-病原体相互作用的图谱。我们的分析确定了一些以前未知的感染特征，例如钾通道和氨基酸转运体的诱导、组蛋白 H3 赖氨酸 27 三甲基化（H3K27me3）标记的基因去抑制以及与上皮-间充质转化（EMT）相关的基因抑制。EMT 基因的抑制依赖于早期病毒基因表达，并与 E-钙黏蛋白（CDH1）和间充质-上皮转化（MET）基因的诱导相关。转化的乳腺癌和神经胶质瘤干细胞的感染也同样抑制 EMT 并诱导 MET，这表明 HCMV 在感染过程中诱导类似上皮的细胞环境。
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