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      Sleep and circadian rhythm disruption alters the lung transcriptome to predispose to viral infection

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          Abstract

          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 characterised. 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.

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          Journal
          Journal ID (nlm-ta): iScience
          Journal ID (iso-abbrev): iScience
          Title: iScience
          Publisher: Elsevier
          ISSN (Electronic): 2589-0042
          Publication date PMC-release: 24 December 2022
          Publication date (Electronic): 24 December 2022
          Electronic Location Identifier: 105877
          Affiliations
          [1 ]Sleep and Circadian Neuroscience Institute (SCNi), Nuffield Department of Clinical Neurosciences, New Biochemistry Building, University of Oxford, South Parks Road, Oxford, OX1 3QU, U.K
          [2 ]Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, U.K
          [3 ]Division of Biomedical Sciences, Warwick Medical School, Interdisciplinary Biomedical Research Building, Gibbet Hill Campus, University of Warwick, Coventry, CV4 7AL, UK
          [4 ]Zeeman Institute for Systems Biology & Infectious Disease Epidemiology Research, Department of Mathematics, Mathematical Sciences Building, University of Warwick, Coventry, CV4 7AL, UK
          [5 ]Nuffield Department of Medicine, University of Oxford, Old Road Campus, Oxford, OX3 7BN, UK
          [6 ]Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Old Road Campus, Oxford, OX3 7BN, UK
          Author notes
          [∗ ]Lead contact AJ
          Article
          Publisher Item ID: S2589-0042(22)02150-2 Publisher ID: 105877
          DOI: 10.1016/j.isci.2022.105877
          PMC ID: 9788990
          PubMed ID: 36590897
          SO-VID: ac59512b-b848-446b-a064-1633105d935f
          Copyright © © 2022.
          License:

          Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

          History
          Date received : 22 March 2022
          Date revision received : 11 October 2022
          Date accepted : 21 December 2022
          Categories
          Subject: Article

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