Cellular responses to human cytomegalovirus infection: Induction of a mesenchymal-to-epithelial transition (MET) phenotype
Cellular responses to human cytomegalovirus infection: Induction of a mesenchymal-to-epithelial transition (MET) phenotype
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DOI：
10.1073/pnas.1710799114
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发表时间：
2017-09-26
影响因子：
11.1
通讯作者：
Shenk, Thomas
中科院分区：
文献类型：
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作者：
Oberstein, Adam;Shenk, Thomas
人巨细胞病毒(HCMV)是典型的人类β-疱疹病毒。在这里，我们使用基因集浓缩分析(GSEA)作为引擎，对HCMV宿主细胞转录组进行系统分析，以全局定位两种细胞类型的宿主与病原体的相互作用。我们的分析发现了几个以前未知的感染特征，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)标记的基因的去抑制，以及与上皮向间充质转化(EMT)相关的基因的抑制。EMT基因的抑制依赖于早期病毒基因的表达，并与诱导E-钙粘蛋白(CDH1)和间充质-上皮转化(MET)基因相关。转化的乳腺癌和胶质瘤干细胞的感染同样抑制EMT和诱导MET，认为HCMV在感染过程中诱导上皮样细胞环境。
Human cytomegalovirus (HCMV) is the prototypical human beta-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.