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

Author

Listed:
  • Xiaodong Zhuang

    (University of Oxford)

  • Andrea Magri

    (University of Oxford)

  • Michelle Hill

    (University of Oxford)

  • Alvina G. Lai

    (University of Oxford)

  • Abhinav Kumar

    (University of Oxford)

  • Srinivasa Bhargav Rambhatla

    (University of Birmingham)

  • Claire L. Donald

    (University of Glasgow)

  • Andrea F. Lopez-Clavijo

    (The Babraham Institute)

  • Simon Rudge

    (The Babraham Institute)

  • Katherine Pinnick

    (University of Oxford)

  • Wai Hoong Chang

    (University of Oxford)

  • Peter A. C. Wing

    (University of Oxford)

  • Ryan Brown

    (University of Birmingham)

  • Ximing Qin

    (Anhui University)

  • Peter Simmonds

    (University of Oxford)

  • Thomas F. Baumert

    (Institut de Recherche sur les Maladies Virales et Hépatiques)

  • David Ray

    (University of Manchester)

  • Andrew Loudon

    (University of Manchester)

  • Peter Balfe

    (University of Birmingham)

  • Michael Wakelam

    (The Babraham Institute)

  • Sam Butterworth

    (University of Manchester)

  • Alain Kohl

    (University of Glasgow)

  • Catherine L. Jopling

    (University of Nottingham)

  • Nicole Zitzmann

    (University of Oxford)

  • Jane A. McKeating

    (University of Oxford)

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.

Suggested Citation

  • 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 , 2019. "The circadian clock components BMAL1 and REV-ERBα regulate flavivirus replication," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08299-7
    DOI: 10.1038/s41467-019-08299-7
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