Format

Send to

Choose Destination
Nat Commun. 2019 Jan 22;10(1):377. doi: 10.1038/s41467-019-08299-7.

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

Author information

1
Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK.
2
Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
3
Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK.
4
MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G61 1QH, UK.
5
The Babraham Institute, Cambridge CB22 3AT, UK.
6
Oxford Centre for Diabetes Endocrinology Metabolism, University of Oxford, Oxford OX3 9DU, UK.
7
Department of Chemistry, University of Birmingham, Birmingham B15 2TT, UK.
8
Institutes of Physical Science and Information Technology, Anhui University, Hefei 230601, China.
9
Inserm U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg 67000, France.
10
Faculty of Medical and Human Sciences, University of Manchester, Manchester M13 9PL, UK.
11
Division of Pharmacy and Optometry, School of Health Sciences, Manchester Academic Health Sciences Centre, University of Manchester, Manchester M13 9NT, UK.
12
School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, UK.
13
Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK. jane.mckeating@ndm.ox.ac.uk.

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.

PMID:
30670689
PMCID:
PMC6343007
DOI:
10.1038/s41467-019-08299-7
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center