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

Abstract

Viruses are intracellular pathogens that hijack host cell machinery and biosynthetic resources to replicate. Rather than being constant, host physiology is rhythmic and undergoes circadian (24 hour) oscillation in a variety of virus-relevant pathways. Whether these daily rhythms impact on viral replication is not known. Here we show that the time of day at which the host is infected regulates virus progression in live mice and in 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 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 thus demonstrates that viruses exploit the clockwork for their own gain, and that the clock therefore represents a novel target for modulating viral replication that extends beyond a single family of these important pathogens.