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Proc Natl Acad Sci U S A. 2016 Sep 6;113(36):10085-90. doi: 10.1073/pnas.1601895113. Epub 2016 Aug 15.

Cell autonomous regulation of herpes and influenza virus infection by the circadian clock.

Author information

1
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;
2
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;
3
Division of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom.
4
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; areddy@cantab.net.

Abstract

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.

KEYWORDS:

circadian; clock; herpes; influenza; virus

PMID:
27528682
PMCID:
PMC5018795
DOI:
10.1073/pnas.1601895113
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors declare no conflict of interest.

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