Cellular responses to human cytomegalovirus infection: Induction of a mesenchymal-to-epithelial transition (MET) phenotype

Adam Oberstein, Thomas Shenk

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Human cytomegalovirus (HCMV) is the prototypical human β-her-pes 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.

Original languageEnglish (US)
Pages (from-to)E8244-E8253
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number39
DOIs
StatePublished - Sep 26 2017

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Cytomegalovirus
  • EMT
  • GSEA
  • MET
  • RNA-seq

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