The circadian clock components BMAL1 and REV-ERB? 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.

doi:10.1038/s41467-019-08299-7

The circadian clock components BMAL1 and REV-ERB? 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

CATHERINE JOPLING catherine.jopling@nottingham.ac.uk
Associate Professor

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.

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), Article 377. https://doi.org/10.1038/s41467-019-08299-7

Journal Article Type	Article
Acceptance Date	Dec 17, 2018
Online Publication Date	Jan 22, 2019
Publication Date	Jan 22, 2019
Deposit Date	Jan 25, 2019
Publicly Available Date	Jan 28, 2019
Journal	Nature Communications
Electronic ISSN	2041-1723
Publisher	Nature Publishing Group
Peer Reviewed	Peer Reviewed
Volume	10
Issue	1
Article Number	377
DOI	https://doi.org/10.1038/s41467-019-08299-7
Keywords	General Biochemistry, Genetics and Molecular Biology; General Physics and Astronomy; General Chemistry
Public URL	https://nottingham-repository.worktribe.com/output/1498014
Publisher URL	https://www.nature.com/articles/s41467-019-08299-7