دورية أكاديمية
Macrophage ACE2 is necessary for SARS-CoV-2 replication and subsequent cytokine responses that restrict continued virion release.
| العنوان: | Macrophage ACE2 is necessary for SARS-CoV-2 replication and subsequent cytokine responses that restrict continued virion release. |
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| المؤلفون: | Labzin LI; Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia.; IMB Centre for Inflammation and Disease Research, University of Queensland, Brisbane, QLD 4072, Australia.; Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD 4072, Australia., Chew KY; School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD 4072, Australia., Eschke K; Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia., Wang X; Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia.; IMB Centre for Inflammation and Disease Research, University of Queensland, Brisbane, QLD 4072, Australia., Esposito T; Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia.; IMB Centre for Inflammation and Disease Research, University of Queensland, Brisbane, QLD 4072, Australia., Stocks CJ; Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia.; IMB Centre for Inflammation and Disease Research, University of Queensland, Brisbane, QLD 4072, Australia., Rae J; Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia.; Centre for Microscopy and Microanalysis, University of Queensland, Brisbane, QLD 4072, Australia., Patrick R; Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia., Mostafavi H; Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia., Hill B; Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia., Yordanov TE; Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia., Holley CL; Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia.; IMB Centre for Inflammation and Disease Research, University of Queensland, Brisbane, QLD 4072, Australia., Emming S; Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia.; IMB Centre for Inflammation and Disease Research, University of Queensland, Brisbane, QLD 4072, Australia., Fritzlar S; Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia., Mordant FL; Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia., Steinfort DP; Department of Medicine, University of Melbourne, Parkville, VIC 3010, Australia.; Department of Respiratory Medicine, Royal Melbourne Hospital, Parkville, VIC 3052, Australia., Subbarao K; Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.; WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia., Nefzger CM; Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia., Lagendijk AK; Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia., Gordon EJ; Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia., Parton RG; Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia.; Centre for Microscopy and Microanalysis, University of Queensland, Brisbane, QLD 4072, Australia., Short KR; Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD 4072, Australia.; School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD 4072, Australia., Londrigan SL; Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia., Schroder K; Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia.; IMB Centre for Inflammation and Disease Research, University of Queensland, Brisbane, QLD 4072, Australia.; Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD 4072, Australia.; School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD 4072, Australia. |
| المصدر: | Science signaling [Sci Signal] 2023 Apr 25; Vol. 16 (782), pp. eabq1366. Date of Electronic Publication: 2023 Apr 25. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101465400 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1937-9145 (Electronic) Linking ISSN: 19450877 NLM ISO Abbreviation: Sci Signal Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, D.C. : American Association for the Advancement of Science |
| مواضيع طبية MeSH: | SARS-CoV-2*/physiology , COVID-19*, Humans ; Angiotensin-Converting Enzyme 2/genetics ; Cytokines ; Peptidyl-Dipeptidase A/genetics ; Peptidyl-Dipeptidase A/metabolism ; Macrophages/metabolism ; Virion/metabolism |
| مستخلص: | Macrophages are key cellular contributors to the pathogenesis of COVID-19, the disease caused by the virus SARS-CoV-2. The SARS-CoV-2 entry receptor ACE2 is present only on a subset of macrophages at sites of SARS-CoV-2 infection in humans. Here, we investigated whether SARS-CoV-2 can enter macrophages, replicate, and release new viral progeny; whether macrophages need to sense a replicating virus to drive cytokine release; and, if so, whether ACE2 is involved in these mechanisms. We found that SARS-CoV-2 could enter, but did not replicate within, ACE2-deficient human primary macrophages and did not induce proinflammatory cytokine expression. By contrast, ACE2 overexpression in human THP-1-derived macrophages permitted SARS-CoV-2 entry, processing and replication, and virion release. ACE2-overexpressing THP-1 macrophages sensed active viral replication and triggered proinflammatory, antiviral programs mediated by the kinase TBK-1 that limited prolonged viral replication and release. These findings help elucidate the role of ACE2 and its absence in macrophage responses to SARS-CoV-2 infection. |
| المشرفين على المادة: | EC 3.4.17.23 (Angiotensin-Converting Enzyme 2) 0 (Cytokines) EC 3.4.15.1 (Peptidyl-Dipeptidase A) |
| تواريخ الأحداث: | Date Created: 20230425 Date Completed: 20230427 Latest Revision: 20230427 |
| رمز التحديث: | 20240829 |
| DOI: | 10.1126/scisignal.abq1366 |
| PMID: | 37098119 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1937-9145 |
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| DOI: | 10.1126/scisignal.abq1366 |