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

Zhuang, X. et al. (2019) The circadian clock components BMAL1 and REV-ERBα regulate flavivirus replication. Nature Communications, 10, (doi: 10.1038/s41467-019-08299-7) (PMID:30670689) (PMCID:PMC6343007)

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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.

Item Type:Articles
Additional Information:Work in the J.A.M. laboratory is funded by: EU 2020 Research and Innovation Programme Consortia HEP-CAR under grant agreement No.667273 and Wellcome Trust IA 200838/Z/16/Z. A.K. was funded by the UK MRC (MC-UU-12014, MR/N017552/1). Work by M.H., A.K. and N.Z. are supported by the Oxford Glycobiology Endowment. D.R. and A.L. are Wellcome Trust investigators 107849/Z/15/Z. M.W. lab is supported by the EU2020 HEP-CAR grant and by the BBSRC (BB/PO13384/1).
Glasgow Author(s) Enlighten ID:Donald, Dr Claire and Kohl, Professor Alain
Authors: Zhuang, X., Magri, A., Hill, M., Lai, A. G., Kumar, A., Rambhatla, S. B., Donald, C. L., Lopez-Clavijo, A. F., Rudge, S., Pinnick, K., Chang, W. H., Wing, P. A. C., Brown, R., Qin, X., Simmonds, P., Baumert, T. F., Ray, D., Loudon, A., Balfe, P., Wakelam, M., Butterworth, S., Kohl, A., Jopling, C. L., Zitzmann, N., and McKeating, J. A.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Nature Communications
Publisher:Nature Publishing Group
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Nature Communications 10:377
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
708681The emergence of Zika virus in Brazil: investigating prevalence and host responses to design preventive strategiesAlain KohlMedical Research Council (MRC)MR/N017552/1MVLS III - CENTRE FOR VIRUS RESEARCH