Edgar Rachel S, Stangherlin Alessandra, Nagy Andras D, Nicoll Michael P, Efstathiou Stacey, O'Neill John S, Reddy Akhilesh B
University of Cambridge Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom;
University of Cambridge Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; Department of Anatomy, University of Pecs Medical School, H-7624 Pecs, Hungary;
Proc Natl Acad Sci U S A. 2016 Sep 6;113(36):10085-90. doi: 10.1073/pnas.1601895113. Epub 2016 Aug 15.
Viruses are intracellular pathogens that hijack host cell machinery and resources to replicate. Rather than being constant, host physiology is rhythmic, undergoing circadian (∼24 h) oscillations in many virus-relevant pathways, but whether daily rhythms impact on viral replication is unknown. We find that the time of day of host infection regulates virus progression in live mice and individual cells. Furthermore, we demonstrate that herpes and influenza A virus infections are enhanced when host circadian rhythms are abolished by disrupting the key clock gene transcription factor Bmal1. Intracellular trafficking, biosynthetic processes, protein synthesis, and chromatin assembly all contribute to circadian regulation of virus infection. Moreover, herpesviruses differentially target components of the molecular circadian clockwork. Our work demonstrates that viruses exploit the clockwork for their own gain and that the clock represents a novel target for modulating viral replication that extends beyond any single family of these ubiquitous pathogens.
病毒是细胞内病原体，它们劫持宿主细胞的机制和资源进行复制。宿主生理并非一成不变，而是有节律的，许多与病毒相关的途径会经历昼夜（约24小时）振荡，但昼夜节律是否会影响病毒复制尚不清楚。我们发现宿主感染的时间会调节活体小鼠和单个细胞中的病毒进程。此外，我们证明，通过破坏关键的生物钟基因转录因子Bmal1来消除宿主昼夜节律时，疱疹病毒和甲型流感病毒感染会增强。细胞内运输、生物合成过程、蛋白质合成和染色质组装都有助于昼夜节律对病毒感染的调节。此外，疱疹病毒会差异性地靶向分子生物钟机制的组成部分。我们的研究表明，病毒利用生物钟机制为自身谋利，而且生物钟代表了一个调节病毒复制的新靶点，这一靶点超越了这些无处不在的病原体中的任何一个单一类别。
