Investigating the function of a novel short ACE2 isoform

Drs Wheway, Blume and Jackson from the University of Southampton were awarded £152,737 by UKRI BBSRC from their rapid response to COVID-19 funds.

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.

https://gtr.ukri.org/projects?ref=BB%2FV019848%2F1