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Interferons and viruses induce a novel primate-specific isoform dACE2 and not the SARS-CoV-2 receptor ACE2

By Olusegun O Onabajo, A. Rouf Banday, Wusheng Yan, Adeola Obajemu, Megan Stanifer, Deanna M Santer, Oscar Florez-Vargas, Helen Piontkivska, Joselin Vargas, Carmon Kee, D. Lorne J. Tyrrell, Juan L. Mendoza, Steeve Boulant, Ludmila Prokunina-Olsson

Posted 20 Jul 2020
bioRxiv DOI: 10.1101/2020.07.19.210955 (published DOI: 10.1038/s41588-020-00731-9)

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. ### Competing Interest Statement The authors have declared no competing interest.

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