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
Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Department of Infectious Diseases, Molecular Virology, University Hospital Heidelberg, Heidelberg, Germany.
bioRxiv. 2020 Jul 20:2020.07.19.210955. doi: 10.1101/2020.07.19.210955.
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.
导致新冠肺炎的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）利用血管紧张素转换酶2（ACE2）进入靶细胞。 已被提议作为一种干扰素刺激基因（ISG）。因此，干扰素诱导的 表达水平变化可能对新冠肺炎易感性或其结果很重要。在这里，我们报告发现了一种新的、灵长类动物特有的 同种型，我们将其命名为 。我们证明 是一种ISG，而 不是。缺乏356个N端氨基酸的dACE2在结合SARS-CoV-2刺突蛋白和作为羧肽酶方面无功能。我们的结果整合了关于 表达的现有知识，并表明在由治疗、炎性肿瘤微环境或病毒共感染产生的高干扰素条件下， 作为ISG类型的诱导不太可能影响SARS-CoV-2的细胞进入并促进感染。
