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Estrogen-related receptor α is required for efficient human cytomegalovirus replication.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2014 Dec 30; Vol. 111 (52), pp. E5706-15. Date of Electronic Publication: 2014 Dec 15. - Publication Year :
- 2014
-
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.
- Subjects :
- Biomarkers, Tumor genetics
Biomarkers, Tumor metabolism
Cell Line
Cytomegalovirus Infections genetics
Cytomegalovirus Infections pathology
DNA-Binding Proteins genetics
DNA-Binding Proteins metabolism
Glycolysis genetics
Hexokinase genetics
Hexokinase metabolism
Humans
Phosphopyruvate Hydratase genetics
Phosphopyruvate Hydratase metabolism
Protein Biosynthesis genetics
RNA, Viral genetics
RNA, Viral metabolism
Triose-Phosphate Isomerase genetics
Triose-Phosphate Isomerase metabolism
Tumor Suppressor Proteins genetics
Tumor Suppressor Proteins metabolism
Cytomegalovirus physiology
Cytomegalovirus Infections metabolism
Estrogen Receptor alpha metabolism
Virus Replication physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 111
- Issue :
- 52
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 25512541
- Full Text :
- https://doi.org/10.1073/pnas.1422361112