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

Jesse Hwang, John G. Purdy, Kai Wu, Joshua D. Rabinowitz, Thomas Eugene Shenk

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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 ERRαactivity. 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.

Original languageEnglish (US)
Pages (from-to)E5706-E5715
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number52
DOIs
StatePublished - Dec 30 2014

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Herpesvirus
  • Mass spectrometry
  • Metabolism
  • Nuclear receptor

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