Title | Cellular responses to human cytomegalovirus infection: Induction of a mesenchymal-to-epithelial transition (MET) phenotype. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Oberstein, A, Shenk, T |
Journal | Proc Natl Acad Sci U S A |
Volume | 114 |
Issue | 39 |
Pagination | E8244-E8253 |
Date Published | 2017 09 26 |
ISSN | 1091-6490 |
Keywords | Antigens, CD, Cadherins, Cell Line, Tumor, Cytomegalovirus, Cytomegalovirus Infections, Epithelial-Mesenchymal Transition, Histones, Humans |
Abstract | <p>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.</p> |
DOI | 10.1073/pnas.1710799114 |
Alternate Journal | Proc Natl Acad Sci U S A |
PubMed ID | 28874566 |
PubMed Central ID | PMC5625929 |
Grant List | F32 AI106175 / AI / NIAID NIH HHS / United States R01 AI112951 / AI / NIAID NIH HHS / United States R56 AI112951 / AI / NIAID NIH HHS / United States |