Estrogen-related receptor α is required for efficient human cytomegalovirus replication. Author Jesse Hwang, John Purdy, Kai Wu, Joshua Rabinowitz, Thomas Shenk Publication Year 2014 Type Journal Article Abstract An shRNA-mediated screen of the 48 human nuclear receptor genes identified multiple candidates likely to influence the production of human cytomegalovirus in cultured human fibroblasts, including the estrogen-related receptor α (ERRα), an orphan nuclear receptor. The 50-kDa receptor and a 76-kDa variant were induced posttranscriptionally following infection. Genetic and pharmacological suppression of the receptor reduced viral RNA, protein, and DNA accumulation, as well as the yield of infectious progeny. In addition, RNAs encoding multiple metabolic enzymes, including enzymes sponsoring glycolysis (enolase 1, triosephosphate isomerase 1, and hexokinase 2), were reduced when the function of ERRα was inhibited in infected cells. Consistent with the effect on RNAs, a substantial number of metabolites, which are normally induced by infection, were either not increased or were increased to a reduced extent in the absence of normal ERRα activity. We conclude that ERRα is needed for the efficient production of cytomegalovirus progeny, and we propose that the nuclear receptor contributes importantly to the induction of a metabolic environment that supports optimal cytomegalovirus replication. Keywords Protein Biosynthesis, RNA, Viral, Humans, Cell Line, DNA-Binding Proteins, Cytomegalovirus, Cytomegalovirus Infections, Virus Replication, Biomarkers, Tumor, Estrogen Receptor alpha, Glycolysis, Hexokinase, Phosphopyruvate Hydratase, Triose-Phosphate Isomerase, Tumor Suppressor Proteins Journal Proc Natl Acad Sci U S A Volume 111 Issue 52 Pages E5706-15 Date Published 2014 Dec 30 ISSN Number 1091-6490 DOI 10.1073/pnas.1422361112 Alternate Journal Proc Natl Acad Sci U S A PMCID PMC4284536 PMID 25512541 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML