The circadian clock components BMAL1 and REV-ERBα regulate flavivirus replication

Xiaodong Zhuang, Andrea Magri, Michelle Hill, Alvina G Lai, Abhinav Kumar, Srinivasa Bhargav Rambhatla, Claire L Donald, Andrea F Lopez-Clavijo, Simon Rudge, Katherine Pinnick, Wai Hoong Chang, Peter A C Wing, Ryan Brown, Ximing Qin, Peter Simmonds, Thomas F Baumert, David Ray, Andrew Loudon, Peter Balfe, Michael WakelamSam Butterworth, Alain Kohl, Catherine L Jopling, Nicole Zitzmann, Jane A McKeating

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)
137 Downloads (Pure)

Abstract

The circadian clock regulates immune responses to microbes and affects pathogen replication, but the underlying molecular mechanisms are not well understood. Here we demonstrate that the circadian components BMAL1 and REV-ERBα influence several steps in the hepatitis C virus (HCV) life cycle, including particle entry into hepatocytes and RNA genome replication. Genetic knock out of Bmal1 and over-expression or activation of REV-ERB with synthetic agonists inhibits the replication of HCV and the related flaviruses dengue and Zika via perturbation of lipid signaling pathways. This study highlights a role for the circadian clock component REV-ERBα in regulating flavivirus replication.

Original languageEnglish
Article number377
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPublished - 22 Jan 2019

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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