title: Estrogen-related receptor α is required for efficient human cytomegalovirus replication.
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.
authors.affiliation: Departments of Molecular Biology and.
authors.forename: Jesse
authors.initials: J
authors.lastname: Hwang
authors.affiliation: Chemistry and the Lewis-Sigler Institute for Integrative Genomics Princeton University, Princeton, NJ 08544.
authors.forename: John G
authors.initials: JG
authors.lastname: Purdy
authors.affiliation: Departments of Molecular Biology and.
authors.forename: Kai
authors.initials: K
authors.lastname: Wu
authors.affiliation: Chemistry and the Lewis-Sigler Institute for Integrative Genomics Princeton University, Princeton, NJ 08544.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Rabinowitz
authors.affiliation: Departments of Molecular Biology and tshenk@princeton.edu.
authors.forename: Thomas
authors.initials: T
authors.lastname: Shenk
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D003587:Cytomegalovirus / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D006019:Glycolysis / Q000235:genetics; D006593:Hexokinase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D010751:Phosphopyruvate Hydratase / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D014305:Triose-Phosphate Isomerase / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology*
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D012367:RNA, Viral; D025521:Tumor Suppressor Proteins; D006593:Hexokinase; C095157:ENO1 protein, human; D010751:Phosphopyruvate Hydratase; D014305:Triose-Phosphate Isomerase
keywords: herpesvirus; mass spectrometry; metabolism; nuclear receptor