Interplay between circadian clock and viral infection

Abstract

The circadian clock underpins most physiological conditions and provides a temporal dimension to our understanding of body and tissue homeostasis. Disruptions of circadian rhythms have been associated with many diseases, including metabolic disorders and cancer. Recent literature highlights a role for the circadian clock to regulate innate and adaptive immune functions that may prime the host response to infectious organisms. Viruses are obligate parasites that rely on host cell synthesis machinery for their own replication, survival and dissemination. Here, we review key findings on how circadian rhythms impact viral infection and how viruses modulate molecular clocks to facilitate their own replication. This emerging area of viral-clock biology research provides a fertile ground for discovering novel anti-viral targets and optimizing immune-based therapies.

Keywords: Circadian rhythms; Infectious disease; Viruses.

Fig. 1

Central clock and peripheral clocks. The mammalian circadian clock consists of the central oscillator, located in the suprachiasmatic nucleus (SCN) of the hypothalamus, and peripheral clocks present in virtually all cells of the body. Light activates photoreceptors in the retina that are connected to the central SCN clock that synchronises and entrains peripheral circadian clocks via neural and endocrine pathways. The interplay between the circadian clocks of man and vectors that carry viral pathogens may impact on their capacity to transmit virus

Fig. 2

Molecular regulation of the circadian system. The master transcription factors CLOCK and BMAL1 form a heterodimer which binds the E-box in the promoter region and induce the expression of various gene products, including REV-ERB, Cryptochrome (CRY) and Period (PER) that supress BMAL1 and CLOCK expression, which constitute a negative feedback loop