Estrogen-related receptor α is required for efficient human cytomegalovirus replication.

TitleEstrogen-related receptor α is required for efficient human cytomegalovirus replication.
Publication TypeJournal Article
Year of Publication2014
AuthorsHwang, J, Purdy, JG, Wu, K, Rabinowitz, JD, Shenk, T
JournalProc Natl Acad Sci U S A
Volume111
Issue52
PaginationE5706-15
Date Published2014 Dec 30
ISSN1091-6490
KeywordsBiomarkers, Tumor, Cell Line, Cytomegalovirus, Cytomegalovirus Infections, DNA-Binding Proteins, Estrogen Receptor alpha, Glycolysis, Hexokinase, Humans, Phosphopyruvate Hydratase, Protein Biosynthesis, RNA, Viral, Triose-Phosphate Isomerase, Tumor Suppressor Proteins, Virus Replication
Abstract

<p>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. </p>

DOI10.1073/pnas.1422361112
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID25512541
PubMed Central IDPMC4284536
Grant ListR01 AI097382 / AI / NIAID NIH HHS / United States