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

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

Authors

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 Wakelam

Sam Butterworth

Alain Kohl

Nicole Zitzmann

Jane A. McKeating



Abstract

© 2019, The Author(s). 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.

Journal Article Type Article
Publication Date Jan 22, 2019
Journal Nature Communications
Electronic ISSN 2041-1723
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 10
Issue 1
Article Number 377
APA6 Citation Zhuang, X., Magri, A., Hill, M., Lai, A. G., Kumar, A., Rambhatla, S. B., …McKeating, J. A. (2019). The circadian clock components BMAL1 and REV-ERBα regulate flavivirus replication. Nature Communications, 10(1), https://doi.org/10.1038/s41467-019-08299-7
DOI https://doi.org/10.1038/s41467-019-08299-7
Keywords General Biochemistry, Genetics and Molecular Biology; General Physics and Astronomy; General Chemistry
Publisher URL https://www.nature.com/articles/s41467-019-08299-7

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