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Macrophage ACE2 is necessary for SARS-CoV-2 replication and subsequent cytokine responses that restrict continued virion release

Authors :
Larisa I. Labzin
Keng Yih Chew
Kathrin Eschke
Xiaohui Wang
Tyron Esposito
Claudia J. Stocks
James Rae
Ralph Patrick
Helen Mostafavi
Brittany Hill
Teodor E. Yordanov
Caroline L. Holley
Stefan Emming
Svenja Fritzlar
Francesca L. Mordant
Daniel P. Steinfort
Kanta Subbarao
Christian M. Nefzger
Anne K. Lagendijk
Emma J. Gordon
Robert G. Parton
Kirsty R. Short
Sarah L. Londrigan
Kate Schroder
Source :
Science Signaling. 16
Publication Year :
2023
Publisher :
American Association for the Advancement of Science (AAAS), 2023.

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.

Details

ISSN :
19379145 and 19450877
Volume :
16
Database :
OpenAIRE
Journal :
Science Signaling
Accession number :
edsair.doi...........d054190d895195ee7dd5dc8146aff1a1
Full Text :
https://doi.org/10.1126/scisignal.abq1366