ACE2 is a membrane protein that regulates the cardiovascular system. Additionally, ACE2 acts as a receptor for host cell infection by human coronaviruses, including SARS-CoV-2 that emerged as the cause of the on-going COVID-19 pandemic and has brought unprecedented burden to economy and health. ACE2 binds the spike protein of SARS-CoV-2 with high affinity and shows little variation in amino acid sequence meaning natural resistance is rare. The discovery of a novel short ACE2 isoform ( delta ACE2) provides evidence for inter-individual differences in SARS-CoV-2 susceptibility and severity, and likelihood of developing subsequent ‘Long COVID’. Critically, delta ACE2 loses SARS-CoV-2 spike protein binding sites in the extracellular domain, and is predicted to confer reduced susceptibility to viral infection. We aimed to assess the differential expression of full-length ACE2 versus delta ACE2 in a panel of human tissues (kidney, heart, lung, and liver) that are implicated in COVID-19, and confirm ACE2 protein in these tissues. Using dual antibody staining, we show that delta ACE2 localises, and is enriched, in lung airway epithelia and bile duct epithelia in the liver. Finally, we also confirm that a fluorescently tagged SARS-CoV-2 spike protein monomer shows low binding at lung and bile duct epithelia where dACE2 is enriched.
【저자키워드】 Translational research, Medical research, 【초록키워드】 COVID-19, SARS-CoV-2, viral infection, ACE2, antibody, susceptibility, COVID-19 pandemic, severity, Variation, Infection, lung, cardiovascular system, binding site, kidney, Health, membrane protein, SARS-CoV-2 spike protein, receptor, liver, human coronaviruses, binding, Amino acid, Evidence, regulate, ACE2 protein, host cell, differential expression, tissues, domain, SARS-CoV-2 susceptibility, sequence, high affinity, monomer, staining, full-length, epithelia, isoform, airway epithelia, likelihood, Extracellular, bind, predicted, subsequent, reduced, human tissue, provide, the spike protein, implicated, inter-individual, 【제목키워드】 SARS-CoV-2, ACE2, Human, viral entry, binding site, expression, receptor ACE2, isoform,