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一种新型的ACE2亚型可在人呼吸道上皮细胞中表达
作者:小柯机器人 发布时间:2021/1/14 15:47:03

英国南安普顿大学Vito Mennella等研究人员合作发现,一种新型的ACE2亚型在人呼吸道上皮细胞中表达,并由于干扰素和RNA呼吸道病毒感染而上调。相关论文于2021年1月21日在线发表在《自然—遗传学》杂志上。

研究人员表示,血管紧张素转换酶2(ACE2)是SARS-CoV-2在气道上皮细胞中的主要进入位点。ACE2与SARS-CoV-2突刺蛋白的结合触发了病毒与细胞质膜的融合,从而导致病毒RNA基因组传递到宿主中。尽管ACE2在SARS-CoV-2感染中起关键作用,但对ACE2表达(包括对病毒感染的反应)的全面了解仍不清楚。ACE2被认为可以编码五种转录物和一种805个氨基酸的蛋白质。

研究人员确定了在呼吸道上皮细胞(SARS-CoV-2感染的主要部位)中表达的ACE2新型短异构体。短ACE2会因干扰素刺激和鼻病毒感染而显著上调,但SARS-CoV-2感染则不会。这种短的同工型缺乏SARS-CoV-2突刺的高亲和力结合位点,并且这些数据完全符合以下模型:短ACE2不太可能直接导致宿主对SARS-CoV-2感染的易感性。

附:英文原文

Title: A novel ACE2 isoform is expressed in human respiratory epithelia and is upregulated in response to interferons and RNA respiratory virus infection

Author: Cornelia Blume, Claire L. Jackson, Cosma Mirella Spalluto, Jelmer Legebeke, Liliya Nazlamova, Franco Conforti, Jeanne-Marie Perotin, Martin Frank, John Butler, Max Crispin, Janice Coles, James Thompson, Robert A. Ridley, Lareb S. N. Dean, Matthew Loxham, Stephanie Reikine, Adnan Azim, Kamran Tariq, David A. Johnston, Paul J. Skipp, Ratko Djukanovic, Diana Baralle, Christopher J. McCormick, Donna E. Davies, Jane S. Lucas, Gabrielle Wheway, Vito Mennella

Issue&Volume: 2021-01-11

Abstract: Angiotensin-converting enzyme 2 (ACE2) is the main entry point in airway epithelial cells for SARS-CoV-2. ACE2 binding to the SARS-CoV-2 protein spike triggers viral fusion with the cell plasma membrane, resulting in viral RNA genome delivery into the host. Despite ACE2’s critical role in SARS-CoV-2 infection, full understanding of ACE2 expression, including in response to viral infection, remains unclear. ACE2 was thought to encode five transcripts and one protein of 805 amino acids. In the present study, we identify a novel short isoform of ACE2 expressed in the airway epithelium, the main site of SARS-CoV-2 infection. Short ACE2 is substantially upregulated in response to interferon stimulation and rhinovirus infection, but not SARS-CoV-2 infection. This short isoform lacks SARS-CoV-2 spike high-affinity binding sites and, altogether, our data are consistent with a model where short ACE2 is unlikely to directly contribute to host susceptibility to SARS-CoV-2 infection.

DOI: 10.1038/s41588-020-00759-x

Source: https://www.nature.com/articles/s41588-020-00759-x

期刊信息

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:25.455
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex