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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

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 L. Jopling, Nicole Zitzmann, Jane A. McKeating

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. More... »

PAGES

377

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41467-019-08299-7

DOI

http://dx.doi.org/10.1038/s41467-019-08299-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1111593706

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30670689


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