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Circadian regulation of SARS-CoV-2 infection in lung epithelial cells
Xiaodong Zhuang; Senko Tsukuda; Florian Wrensch; Peter AC Wing; Mirjam Schilling; James M Harris; Helene Borrmann; Sophie B Morgan; Jennifer L Cane; Laurent Mailly; Nazia Thakur; Carina Conceicao; Harshmeena Sanghani; Laura Heydmann; Charlotte Bach; Anna Ashton; Steven Walsh; Tiong Kit Tan; Lisa Schimanski; Kuan-Ying A Huang; Catherine Schuster; Koichi Watashi; Timothy SC Hinks; Aarti Jagannath; Sridhar R Vausdevan; Dalan Bailey; Thomas F Baumert; Jane A McKeating.
Affiliation
  • Xiaodong Zhuang; Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Senko Tsukuda; Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Florian Wrensch; Universite de Strasbourg, Strasbourg, France and INSERM, U1110, Institut de Recherche sur les Maladies Virales et Hepatiques, Strasbourg, France.
  • Peter AC Wing; Nuffield Department of Medicine, University of Oxford, Oxford, UK; Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxfo
  • Mirjam Schilling; Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • James M Harris; Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Helene Borrmann; Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Sophie B Morgan; Respiratory Medicine Unit and National Institute for Health Research Oxford Biomedical Research Centre, Nuffield Department of Medicine, Experimental Medicine,
  • Jennifer L Cane; Respiratory Medicine Unit and National Institute for Health Research Oxford Biomedical Research Centre, Nuffield Department of Medicine, Experimental Medicine,
  • Laurent Mailly; Universite de Strasbourg, Strasbourg, France and INSERM, U1110, Institut de Recherche sur les Maladies Virales et Hepatiques, Strasbourg, France.
  • Nazia Thakur; The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey, UK.
  • Carina Conceicao; The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey, UK.
  • Harshmeena Sanghani; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
  • Laura Heydmann; Universite de Strasbourg, Strasbourg, France and INSERM, U1110, Institut de Recherche sur les Maladies Virales et Hepatiques, Strasbourg, France.
  • Charlotte Bach; Universite de Strasbourg, Strasbourg, France and INSERM, U1110, Institut de Recherche sur les Maladies Virales et Hepatiques, Strasbourg, France
  • Anna Ashton; Department of Pharmacology, University of Oxford, Oxford, UK
  • Steven Walsh; Department of Pharmacology, University of Oxford, Oxford, UK.
  • Tiong Kit Tan; MRC Human Immunology Unit, MRC Weatherall Institute, John Radcliffe Hospital, Oxford 17 OX3 9DS, UK.
  • Lisa Schimanski; Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK; MRC Human Immunology Unit, MRC Weatherall Institute, John R
  • Kuan-Ying A Huang; Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University and Division of Pediatric Infectious Diseases, Department of Pediatric
  • Catherine Schuster; Universite de Strasbourg, Strasbourg, France and INSERM, U1110, Institut de Recherche sur les Maladies Virales et Hepatiques, Strasbourg, France.
  • Koichi Watashi; Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640, Japan; Department of Applied Biological Science, Tokyo University of Scien
  • Timothy SC Hinks; Respiratory Medicine Unit and National Institute for Health Research Oxford Biomedical Research Centre, Nuffield Department of Medicine, Experimental Medicine,
  • Aarti Jagannath; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
  • Sridhar R Vausdevan; Department of Pharmacology, University of Oxford, Oxford, UK.
  • Dalan Bailey; The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey, UK.
  • Thomas F Baumert; Universite de Strasbourg, Strasbourg, France and INSERM, U1110, Institut de Recherche sur les Maladies Virales et Hepatiques, Strasbourg, France; . Pole Hepato-
  • Jane A McKeating; Nuffield Department of Medicine, University of Oxford, Oxford, UK; Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxfo
Preprint in English | bioRxiv | ID: ppbiorxiv-436163
ABSTRACT
The COVID-19 pandemic, caused by SARS-CoV-2 coronavirus, is a global health issue with unprecedented challenges for public health. SARS-CoV-2 primarily infects cells of the respiratory tract, via Spike glycoprotein binding angiotensin-converting enzyme (ACE2). Circadian rhythms coordinate an organisms response to its environment and can regulate host susceptibility to virus infection. We demonstrate a circadian regulation of ACE2 in lung epithelial cells and show that silencing BMAL1 or treatment with a synthetic REV-ERB agonist SR9009 reduces ACE2 expression and inhibits SARS-CoV-2 entry. Treating infected cells with SR9009 limits viral replication and secretion of infectious particles, showing that post-entry steps in the viral life cycle are influenced by the circadian system. Transcriptome analysis revealed that Bmal1 silencing induced a wide spectrum of interferon stimulated genes in Calu-3 lung epithelial cells, providing a mechanism for the circadian pathway to dampen SARS-CoV-2 infection. Our study suggests new approaches to understand and improve therapeutic targeting of SARS-CoV-2.
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Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2021 Document type: Preprint
Fulltext
Add to My VHL
Print
XML
Search on Google
Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2021 Document type: Preprint