Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK.
Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
Nat Commun. 2019 Jan 22;10(1):377. doi: 10.1038/s41467-019-08299-7.
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.
生物钟调节对微生物的免疫反应并影响病原体的复制，但其中的分子机制尚不清楚。本研究表明，生物钟成分 BMAL1 和 REV-ERBα 影响丙型肝炎病毒 (HCV) 生命周期的几个步骤，包括颗粒进入肝细胞和 RNA 基因组复制。通过对脂质信号通路的干扰，Bmal1 的基因敲除以及 REV-ERB 的过表达或合成激动剂的激活均抑制了 HCV 以及相关黄病毒登革热和寨卡病毒的复制。本研究强调了生物钟成分 REV-ERBα 在调节黄病毒复制中的作用。
