The circadian clock component BMAL1 regulates SARS-CoV-2 entry and replication in lung epithelial cells
The coronavirus disease 2019 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (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 to angiotens...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Cell Press
2021
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| _version_ | 1797073132662554624 |
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| author | Zhuang, X Tsukuda, S Wrensch, F Wing, PAC Schilling, M Harris, JM Borrmann, H Morgan, SB Cane, JL Mailly, L Thakur, N Conceicao, C Sanghani, H Heydmann, L Bach, C Ashton, A Walsh, S Tan, TK Schimanski, L Huang, K-YA Schuster, C Watashi, K Hinks, TSC Jagannath, A Vausdevan, SR Bailey, D Baumert, TF McKeating, JA |
| author_facet | Zhuang, X Tsukuda, S Wrensch, F Wing, PAC Schilling, M Harris, JM Borrmann, H Morgan, SB Cane, JL Mailly, L Thakur, N Conceicao, C Sanghani, H Heydmann, L Bach, C Ashton, A Walsh, S Tan, TK Schimanski, L Huang, K-YA Schuster, C Watashi, K Hinks, TSC Jagannath, A Vausdevan, SR Bailey, D Baumert, TF McKeating, JA |
| author_sort | Zhuang, X |
| collection | OXFORD |
| description | The coronavirus disease 2019 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (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 to angiotensin-converting enzyme (ACE2). Circadian rhythms coordinate an organism's response to its environment and can regulate host susceptibility to virus infection. We demonstrate that silencing the circadian regulator Bmal1 or treating lung epithelial cells with the REV-ERB agonist SR9009 reduces ACE2 expression and inhibits SARS-CoV-2 entry and replication. Importantly, treating infected cells with SR9009 limits SARS-CoV-2 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 interferon-stimulated gene transcripts in Calu-3 lung epithelial cells, providing a mechanism for the circadian pathway to limit SARS-CoV-2 infection. Our study highlights alternative approaches to understand and improve therapeutic targeting of SARS-CoV-2. |
| first_indexed | 2024-03-06T23:17:39Z |
| format | Journal article |
| id | oxford-uuid:67ab03a5-cc20-4728-8cdc-1617f713d6da |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:17:39Z |
| publishDate | 2021 |
| publisher | Cell Press |
| record_format | dspace |
| spelling | oxford-uuid:67ab03a5-cc20-4728-8cdc-1617f713d6da2022-03-26T18:39:56ZThe circadian clock component BMAL1 regulates SARS-CoV-2 entry and replication in lung epithelial cellsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:67ab03a5-cc20-4728-8cdc-1617f713d6daEnglishSymplectic ElementsCell Press2021Zhuang, XTsukuda, SWrensch, FWing, PACSchilling, MHarris, JMBorrmann, HMorgan, SBCane, JLMailly, LThakur, NConceicao, CSanghani, HHeydmann, LBach, CAshton, AWalsh, STan, TKSchimanski, LHuang, K-YASchuster, CWatashi, KHinks, TSCJagannath, AVausdevan, SRBailey, DBaumert, TFMcKeating, JAThe coronavirus disease 2019 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (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 to angiotensin-converting enzyme (ACE2). Circadian rhythms coordinate an organism's response to its environment and can regulate host susceptibility to virus infection. We demonstrate that silencing the circadian regulator Bmal1 or treating lung epithelial cells with the REV-ERB agonist SR9009 reduces ACE2 expression and inhibits SARS-CoV-2 entry and replication. Importantly, treating infected cells with SR9009 limits SARS-CoV-2 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 interferon-stimulated gene transcripts in Calu-3 lung epithelial cells, providing a mechanism for the circadian pathway to limit SARS-CoV-2 infection. Our study highlights alternative approaches to understand and improve therapeutic targeting of SARS-CoV-2. |
| spellingShingle | Zhuang, X Tsukuda, S Wrensch, F Wing, PAC Schilling, M Harris, JM Borrmann, H Morgan, SB Cane, JL Mailly, L Thakur, N Conceicao, C Sanghani, H Heydmann, L Bach, C Ashton, A Walsh, S Tan, TK Schimanski, L Huang, K-YA Schuster, C Watashi, K Hinks, TSC Jagannath, A Vausdevan, SR Bailey, D Baumert, TF McKeating, JA The circadian clock component BMAL1 regulates SARS-CoV-2 entry and replication in lung epithelial cells |
| title | The circadian clock component BMAL1 regulates SARS-CoV-2 entry and replication in lung epithelial cells |
| title_full | The circadian clock component BMAL1 regulates SARS-CoV-2 entry and replication in lung epithelial cells |
| title_fullStr | The circadian clock component BMAL1 regulates SARS-CoV-2 entry and replication in lung epithelial cells |
| title_full_unstemmed | The circadian clock component BMAL1 regulates SARS-CoV-2 entry and replication in lung epithelial cells |
| title_short | The circadian clock component BMAL1 regulates SARS-CoV-2 entry and replication in lung epithelial cells |
| title_sort | circadian clock component bmal1 regulates sars cov 2 entry and replication in lung epithelial cells |
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