Your browser doesn't support javascript.
Macrophage ACE2 is necessary for SARS-CoV-2 replication and subsequent cytokine responses that restrict continued virion release.
Labzin, Larisa I; Chew, Keng Yih; Eschke, Kathrin; Wang, Xiaohui; Esposito, Tyron; Stocks, Claudia J; Rae, James; Patrick, Ralph; Mostafavi, Helen; Hill, Brittany; Yordanov, Teodor E; Holley, Caroline L; Emming, Stefan; Fritzlar, Svenja; Mordant, Francesca L; Steinfort, Daniel P; Subbarao, Kanta; Nefzger, Christian M; Lagendijk, Anne K; Gordon, Emma J; Parton, Robert G; Short, Kirsty R; Londrigan, Sarah L; Schroder, Kate.
  • Labzin LI; Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia.
  • Chew KY; IMB Centre for Inflammation and Disease Research, University of Queensland, Brisbane, QLD 4072, Australia.
  • Eschke K; Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD 4072, Australia.
  • Wang X; School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD 4072, Australia.
  • Esposito T; Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia.
  • Stocks CJ; Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia.
  • Rae J; IMB Centre for Inflammation and Disease Research, University of Queensland, Brisbane, QLD 4072, Australia.
  • Patrick R; Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia.
  • Mostafavi H; IMB Centre for Inflammation and Disease Research, University of Queensland, Brisbane, QLD 4072, Australia.
  • Hill B; Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia.
  • Yordanov TE; IMB Centre for Inflammation and Disease Research, University of Queensland, Brisbane, QLD 4072, Australia.
  • Holley CL; Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia.
  • Emming S; Centre for Microscopy and Microanalysis, University of Queensland, Brisbane, QLD 4072, Australia.
  • Fritzlar S; Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia.
  • Mordant FL; Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia.
  • Steinfort DP; Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia.
  • Subbarao K; Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia.
  • Nefzger CM; Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia.
  • Lagendijk AK; IMB Centre for Inflammation and Disease Research, University of Queensland, Brisbane, QLD 4072, Australia.
  • Gordon EJ; Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia.
  • Parton RG; IMB Centre for Inflammation and Disease Research, University of Queensland, Brisbane, QLD 4072, Australia.
  • Short KR; Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, 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; Department of Medicine, University of Melbourne, Parkville, VIC 3010, Australia.
Sci Signal ; 16(782): eabq1366, 2023 04 25.
Article in English | MEDLINE | ID: covidwho-2298370
ABSTRACT
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.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Limits: Humans Language: English Journal: Sci Signal Journal subject: Science / Physiology Year: 2023 Document Type: Article Affiliation country: Scisignal.abq1366

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Limits: Humans Language: English Journal: Sci Signal Journal subject: Science / Physiology Year: 2023 Document Type: Article Affiliation country: Scisignal.abq1366