The circadian clock components BMAL1 and REV-ERBα regulate flavivirus replication.
Fiche publication
Date publication
janvier 2019
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BAUMERT Thomas
Tous les auteurs :
Zhuang X, Magri A, Hill M, Lai AG, Kumar A, Rambhatla SB, Donald CL, Lopez-Clavijo AF, Rudge S, Pinnick K, Chang WH, Wing PAC, Brown R, Qin X, Simmonds P, Baumert TF, Ray D, Loudon A, Balfe P, Wakelam M, Butterworth S, Kohl A, Jopling CL, Zitzmann N, McKeating JA
Lien Pubmed
Résumé
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.
Mots clés
ARNTL Transcription Factors, genetics, Cell Line, Circadian Clocks, genetics, DNA Replication, Dengue, Dengue Virus, drug effects, Flavivirus, drug effects, Gene Expression Regulation, genetics, Genes, Essential, genetics, Hepacivirus, drug effects, Hepatitis C, Hepatocytes, immunology, Humans, Nuclear Receptor Subfamily 1, Group D, Member 1, genetics, Proteomics, RNA, Messenger, metabolism, Virus Internalization, drug effects, Virus Replication, drug effects, Zika Virus, drug effects, Zika Virus Infection
Référence
Nat Commun. 2019 Jan 22;10(1):377