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.

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