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. has been proposed as an interferon-stimulated gene (ISG). Thus, interferon-induced variability in expression levels could be important for...

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Published inbioRxiv
Main Authors Onabajo, Olusegun O, Banday, A Rouf, Yan, Wusheng, Obajemu, Adeola, Stanifer, Megan L, Santer, Deanna M, Florez-Vargas, Oscar, Piontkivska, Helen, Vargas, Joselin, Kee, Carmon, Tyrrell, D Lorne J, Mendoza, Juan L, Boulant, Steeve, Prokunina-Olsson, Ludmila
Format Journal Article Paper
LanguageEnglish
Published United States Cold Spring Harbor Laboratory Press 20.07.2020
Subjects
ACE2
Angiotensin
Angiotensin-converting enzyme 2
Carboxypeptidase
Coronaviruses
COVID-19
Inflammation
Interferon
Peptidyl-dipeptidase A
Severe acute respiratory syndrome coronavirus 2
Spike protein
COVID-19
Interferon-stimulated gene
ACE2
SARS-CoV-2
Interferon
immune response
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Summary:Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes COVID-19, utilizes angiotensin-converting enzyme 2 (ACE2) for entry into target cells. has been proposed as an interferon-stimulated gene (ISG). Thus, interferon-induced variability in 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 , which we designate as . We demonstrate that , but not , is an ISG. , 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 expression and suggest that the ISG-type induction of 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.
DOI:10.1101/2020.07.19.210955