Identifying binding partners, biological substrates and antisense oligonucleotides regulating expression of short and long ACE2.

ACE 2是SARS-CoV-2的主要病毒进入点。我们和其他人最近已经证明，两种形式的ACE 2，短和长，在气道上皮细胞中表达，这些表达是独立的启动子的控制下，与短ACE 2强烈诱导IFN。短ACE 2缺乏与SARS-CoV-2刺突结合的高亲和力结合残基，表明它不能与SARS-CoV-2结合。初步研究表明，短ACE 2比长ACE 2更不稳定。短型ACE 2具有跨膜结构域，但没有信号肽，短型ACE 2是否位于膜上及其转运机制尚不清楚。作为一种新发现的分子，人们对短ACE 2的生理功能及其在SARS-CoV-2感染中的作用知之甚少。在这个项目中，我们的目的是确定短和长ACE 2的结合伙伴和生物底物，并调查是否可以修改SARS冠状病毒-2的呼吸道上皮细胞模型中的细胞模型中的反义寡核苷酸的表达的调制短和长ACE 2。

ACE2 is the main viral entry point for SARS-CoV-2. We and others have recently demonstrated that two forms of ACE2, short and long, are expressed in airway epithelial cells, and that expression of these is under the control of independent promoters, with short ACE2 being strongly induced by IFN. Both are upregulated in response to rhinovirus infection but not SARS-CoV-2 infection.Short ACE2 lacks the high affinity binding residues for SARS-CoV-2 spike binding, suggesting that it is not capable of SARS-CoV-2 binding. Preliminary work suggests that short ACE2 is less stable than long ACE2. Short ACE2 has a transmembrane domain but no signal peptide, and it remains unclear whether short ACE2 is located in the membrane and the mechanism of transport of ACE2. As a recently discovered molecule, little is understood about the physiological function of short ACE2 and its role in SARS-CoV-2 infectivity. In this project we aim to identify the binding partners and biological substrates of short and long ACE2 and investigate whether modulation of expression of short and long ACE2 with antisense olignucleotides can modify SARS-CoV-2 infectivity in cell models of respiratory epithelium.