Cell autonomous regulation of herpes and influenza virus infection by the circadian clock
Cell autonomous regulation of herpes and influenza virus infection by the circadian clock
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DOI：
10.1073/pnas.1601895113
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发表时间：
2016-09-06
影响因子：
11.1
通讯作者：
Reddy, Akhilesh B.
中科院分区：
文献类型：
--
作者：
Edgar, Rachel S.;Stangherlin, Alessandra;Reddy, Akhilesh B.
病毒是细胞内的病原体，劫持宿主细胞机器和资源进行复制。而不是恒定的，主机的生理是有节奏的，经历昼夜节律（类似于24小时）振荡在许多病毒相关的途径，但是否每天的节奏影响病毒复制是未知的。我们发现宿主感染的时间调节活小鼠和单个细胞中的病毒进展。此外，我们证明，当宿主的昼夜节律被破坏的关键时钟基因转录因子Bmal1时，疱疹和流感病毒A感染增强。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病毒感染的昼夜调节。此外，疱疹病毒的靶向分子昼夜节律的组成部分不同。我们的工作表明，病毒利用时钟为自己的利益，时钟代表了一个新的目标，用于调节病毒复制，扩展到这些无处不在的病原体的任何单一的家庭。
Viruses are intracellular pathogens that hijack host cell machinery and resources to replicate. Rather than being constant, host physiology is rhythmic, undergoing circadian (similar to 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 enhancedwhen 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.