Taylor Lewis, Von Lendenfeld Felix, Ashton Anna, Sanghani Harshmeena, Di Pretoro Simona, Usselmann Laura, Veretennikova Maria, Dallmann Robert, McKeating Jane A, Vasudevan Sridhar, Jagannath Aarti
Sleep and Circadian Neuroscience Institute (SCNi), Nuffield Department of Clinical Neurosciences, New Biochemistry Building, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK.
iScience. 2023 Feb 17;26(2):105877. doi: 10.1016/j.isci.2022.105877. Epub 2022 Dec 24.
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.
睡眠和昼夜节律紊乱（SCRD），如在轮班工作中所遇到的那样，会增加包括新型冠状病毒（SARS-CoV-2）在内的呼吸道病毒感染风险。然而，SCRD后呼吸道病毒感染率较高的潜在机制仍不清楚。为了解决这个问题，我们研究了急性睡眠剥夺对小鼠肺转录组的影响。我们在此表明，睡眠剥夺会深刻改变肺的转录格局，导致先天和适应性免疫系统均受到抑制，扰乱昼夜节律时钟，并激活与SARS-CoV-2复制相关的基因，从而产生一个可能促进病毒感染及相关疾病发病机制的肺环境。我们的研究为SCRD如何增加包括SARS-CoV-2在内的呼吸道病毒感染风险提供了一种机制解释，并突出了预防和治疗呼吸道病毒感染的可能治疗途径。
