The circadian clock components BMAL1 and REV-ERBα regulate flavivirus replication.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30670689.
- Also identified by DOI 10.1038/s41467-019-08299-7 and PMC identifier 6343007.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- ARNTL Transcription Factors
- Circadian Clocks
- Flavivirus
- Nuclear Receptor Subfamily 1, Group D, Member 1
- Virus Replication