Interferons and viruses induce a novel primate-specific isoform dACE2 and not the SARS-CoV-2 receptor ACE2
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes COVID-19, utilizes angiotensin-converting enzyme 2 (ACE2) for entry into target cells. ACE2 has been proposed as an interferon-stimulated gene (ISG). Thus, interferon-induced variability in ACE2 expression levels could be important for susceptibility to COVID-19 or its outcomes. Here, we report the discovery of a novel, primate-specific isoform of ACE2, which we designate as deltaACE2 (dACE2). We demonstrate that dACE2, but not ACE2, is an ISG. In vitro, dACE2, which lacks 356 N-terminal amino acids, was non-functional in binding the SARS-CoV-2 spike protein and as a carboxypeptidase. Our results reconcile current knowledge on ACE2 expression and suggest that the ISG-type induction of dACE2 in IFN-high conditions created by treatments, inflammatory tumor microenvironment, or viral co-infections is unlikely to affect the cellular entry of SARS-CoV-2 and promote infection.
| Errataetall: | |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2020 |
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| Enthalten in: |
bioRxiv : the preprint server for biology - (2020) vom: 20. Juli |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Onabajo, Olusegun O [VerfasserIn] |
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| Links: |
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| Themen: |
ACE2 |
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| Anmerkungen: |
Date Revised 16.08.2022 published: Electronic UpdateIn: Nat Genet. 2020 Oct 19;:. - PMID 33077916 Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1101/2020.07.19.210955 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM313189374 |
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| 100 | 1 | |a Onabajo, Olusegun O |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Interferons and viruses induce a novel primate-specific isoform dACE2 and not the SARS-CoV-2 receptor ACE2 |
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| 500 | |a Date Revised 16.08.2022 | ||
| 500 | |a published: Electronic | ||
| 500 | |a UpdateIn: Nat Genet. 2020 Oct 19;:. - PMID 33077916 | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes COVID-19, utilizes angiotensin-converting enzyme 2 (ACE2) for entry into target cells. ACE2 has been proposed as an interferon-stimulated gene (ISG). Thus, interferon-induced variability in ACE2 expression levels could be important for susceptibility to COVID-19 or its outcomes. Here, we report the discovery of a novel, primate-specific isoform of ACE2, which we designate as deltaACE2 (dACE2). We demonstrate that dACE2, but not ACE2, is an ISG. In vitro, dACE2, which lacks 356 N-terminal amino acids, was non-functional in binding the SARS-CoV-2 spike protein and as a carboxypeptidase. Our results reconcile current knowledge on ACE2 expression and suggest that the ISG-type induction of dACE2 in IFN-high conditions created by treatments, inflammatory tumor microenvironment, or viral co-infections is unlikely to affect the cellular entry of SARS-CoV-2 and promote infection | ||
| 650 | 4 | |a Preprint | |
| 650 | 4 | |a ACE2 | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a Interferon | |
| 650 | 4 | |a Interferon-stimulated gene | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a immune response | |
| 700 | 1 | |a Banday, A Rouf |e verfasserin |4 aut | |
| 700 | 1 | |a Yan, Wusheng |e verfasserin |4 aut | |
| 700 | 1 | |a Obajemu, Adeola |e verfasserin |4 aut | |
| 700 | 1 | |a Stanifer, Megan L |e verfasserin |4 aut | |
| 700 | 1 | |a Santer, Deanna M |e verfasserin |4 aut | |
| 700 | 1 | |a Florez-Vargas, Oscar |e verfasserin |4 aut | |
| 700 | 1 | |a Piontkivska, Helen |e verfasserin |4 aut | |
| 700 | 1 | |a Vargas, Joselin |e verfasserin |4 aut | |
| 700 | 1 | |a Kee, Carmon |e verfasserin |4 aut | |
| 700 | 1 | |a Tyrrell, D Lorne J |e verfasserin |4 aut | |
| 700 | 1 | |a Mendoza, Juan L |e verfasserin |4 aut | |
| 700 | 1 | |a Boulant, Steeve |e verfasserin |4 aut | |
| 700 | 1 | |a Prokunina-Olsson, Ludmila |e verfasserin |4 aut | |
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