The circadian clock components BMAL1 and REV-ERBα regulate flavivirus replication.
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Peer-reviewed
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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.
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Keywords
ARNTL Transcription Factors, Cell Line, Circadian Clocks, DNA Replication, Dengue, Dengue Virus, Flavivirus, Gene Expression Regulation, Genes, Essential, Hepacivirus, Hepatitis C, Hepatocytes, Humans, Nuclear Receptor Subfamily 1, Group D, Member 1, Proteomics, RNA, Messenger, Virus Internalization, Virus Replication, Zika Virus, Zika Virus Infection
Journal Title
Nat Commun
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2041-1723
2041-1723
2041-1723
Volume Title
10
Publisher
Springer Science and Business Media LLC