Sleep and circadian rhythm disruption alters the lung transcriptome to predispose to viral infection
Lewis Taylor,
Felix Von Lendenfeld,
Anna Ashton,
Harshmeena Sanghani,
Simona Di Pretoro,
Laura Usselmann,
Maria Veretennikova,
Robert Dallmann,
Jane A. McKeating,
Sridhar Vasudevan,
Aarti Jagannath
Affiliations
Lewis Taylor
Sleep and Circadian Neuroscience Institute (SCNi), Nuffield Department of Clinical Neurosciences, New Biochemistry Building, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
Felix Von Lendenfeld
Sleep and Circadian Neuroscience Institute (SCNi), Nuffield Department of Clinical Neurosciences, New Biochemistry Building, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
Anna Ashton
Sleep and Circadian Neuroscience Institute (SCNi), Nuffield Department of Clinical Neurosciences, New Biochemistry Building, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
Harshmeena Sanghani
Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK
Simona Di Pretoro
Sleep and Circadian Neuroscience Institute (SCNi), Nuffield Department of Clinical Neurosciences, New Biochemistry Building, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
Laura Usselmann
Division of Biomedical Sciences, Warwick Medical School, Interdisciplinary Biomedical Research Building, Gibbet Hill Campus, University of Warwick, Coventry CV4 7AL, UK
Maria Veretennikova
Zeeman Institute for Systems Biology & Infectious Disease Epidemiology Research, Department of Mathematics, Mathematical Sciences Building, University of Warwick, Coventry CV4 7AL, UK
Robert Dallmann
Division of Biomedical Sciences, Warwick Medical School, Interdisciplinary Biomedical Research Building, Gibbet Hill Campus, University of Warwick, Coventry CV4 7AL, UK
Jane A. McKeating
Nuffield Department of Medicine, University of Oxford, Old Road Campus, Oxford OX3 7BN, UK; Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Old Road Campus, Oxford OX3 7BN, UK
Sridhar Vasudevan
Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK
Aarti Jagannath
Sleep and Circadian Neuroscience Institute (SCNi), Nuffield Department of Clinical Neurosciences, New Biochemistry Building, University of Oxford, South Parks Road, Oxford OX1 3QU, UK; Corresponding author
Summary: Sleep and circadian rhythm disruption (SCRD), as encountered during shift work, increases the risk of respiratory viral infection including SARS-CoV-2. However, the mechanism(s) underpinning higher rates of respiratory viral infection following SCRD remain poorly characterized. To address this, we investigated the effects of acute sleep deprivation on the mouse lung transcriptome. Here we show that sleep deprivation profoundly alters the transcriptional landscape of the lung, causing the suppression of both innate and adaptive immune systems, disrupting the circadian clock, and activating genes implicated in SARS-CoV-2 replication, thereby generating a lung environment that could promote viral infection and associated disease pathogenesis. Our study provides a mechanistic explanation of how SCRD increases the risk of respiratory viral infections including SARS-CoV-2 and highlights possible therapeutic avenues for the prevention and treatment of respiratory viral infection.
