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

Department of Biological Sciences
  1. Open Access Kent State
  2. Kent State University COVID-19 research and funded grants
  3. Interferons and viruses induce a novel primate-specific isoform dACE2 and not the SARS-CoV-2 receptor ACE2
Author(s)
Abstract

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, transcriptionally independent truncated isoform of ACE2, which we designate as deltaACE2 (dACE2). We demonstrate that dACE2, but not ACE2, is an ISG. In The Cancer Genome Atlas, the expression of dACE2 was enriched in squamous tumors of the respiratory, gastrointestinal and urogenital tracts. In vitro, dACE2, which lacks 356 amino-terminal amino acids, was non-functional in binding the SARS-CoV-2 spike protein and as a carboxypeptidase. Our results suggest that the ISG-type induction of dACE2 in IFN-high conditions created by treatments, an inflammatory tumor microenvironment or viral co-infections is unlikely to increase the cellular entry of SARS-CoV-2 and promote infection.

 

Preprint available here on biorxiv: https://doi.org/10.1101/2020.07.19.210955
Format
Article
Identifier(s)
10.1038/s41588-020-00731-9
Publication Date
2020-10
Publication Title
Nature
Publisher
Nature Genetics
Keywords
Subject
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Department of Biological Sciences
Permalink https://oaks.kent.edu/covid19ksu/interferons-and-viruses-induce-novel-primate-specific-isoform-dace2-and-not-sars-cov-2
Piontkivska, H., Onabajo, O., Banday, A., Yan, W., Obajemu, A., Stanifer, M., Santer, D., Florez-Vargas, O., Vargas-Porras, C., Kee, C., Tyrrell, D., Mendoza, J., Boulant, S., & Prokunina-Olsson, L. (2020). Interferons and viruses induce a novel primate-specific isoform dACE2 and not the SARS-CoV-2 receptor ACE2 (1–). Nature. https://doi.org/https://doi.org/10.1038/s41588-020-00731-9
Piontkivska, Helen, Olusegun Onabajo, A. Banday, Wusheng Yan, Adeola Obajemu, Megan Stanifer, Deanna Santer, et al. 2020. “Interferons and Viruses Induce a Novel Primate-Specific Isoform DACE2 and Not the SARS-CoV-2 Receptor ACE2”. Nature. https://doi.org/https://doi.org/10.1038/s41588-020-00731-9.
Piontkivska, Helen, et al. Interferons and Viruses Induce a Novel Primate-Specific Isoform DACE2 and Not the SARS-CoV-2 Receptor ACE2. Nature, Oct. 2020, https://doi.org/https://doi.org/10.1038/s41588-020-00731-9.