The circadian clock components BMAL1 and REV-ERBα regulate flavivirus replication.
Xiaodong ZhuangAndrea MagriMichelle HillAlvina G LaiAbhinav KumarSrinivasa Bhargav RambhatlaClaire L DonaldAndrea F Lopez-ClavijoSimon RudgeKatherine PinnickWai Hoong ChangPeter A C WingRyan BrownXiming QinPeter SimmondsThomas F BaumertDavid W RayAndrew LoudonPeter BalfeMichael WakelamSam ButterworthAlain KohlCatherine L JoplingNicole ZitzmannJane A McKeatingPublished in: Nature communications (2019)
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.
Keyphrases
- hepatitis c virus
- immune response
- human immunodeficiency virus
- zika virus
- life cycle
- signaling pathway
- poor prognosis
- dengue virus
- aedes aegypti
- genome wide
- gene expression
- dendritic cells
- dna methylation
- epithelial mesenchymal transition
- drug induced
- candida albicans
- pi k akt
- liver injury
- oxidative stress
- cell proliferation
- nucleic acid