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

TitleCellular responses to human cytomegalovirus infection: Induction of a mesenchymal-to-epithelial transition (MET) phenotype.
Publication TypeJournal Article
Year of Publication2017
AuthorsOberstein, A, Shenk, T
JournalProc Natl Acad Sci U S A
Volume114
Issue39
PaginationE8244-E8253
Date Published2017 Sep 26
ISSN1091-6490
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.

DOI10.1073/pnas.1710799114
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID28874566
PubMed Central IDPMC5625929
Grant ListF32 AI106175 / AI / NIAID NIH HHS / United States
R01 AI112951 / AI / NIAID NIH HHS / United States