Cell Autonomous Regulation of Herpes and Influenza Virus Infection by the Circadian Clock

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2016 Aug 17

PMID 27528682

Citations 120

Authors

Rachel S Edgar

Alessandra Stangherlin

Andras D Nagy

Michael P Nicoll

Stacey Efstathiou

John S ONeill

Akhilesh B Reddy

Affiliations

Soon will be listed here.

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.

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