A novel isoform of ACE2 is expressed in human nasal and bronchial respiratory epithelia and is upregulated in response to RNA respiratory virus infection

Blume, C.; Jackson, C. L.; Spalluto, C. M.; Legebeke, J.; Nazlamova, L. A.; Conforti, F.; Perotin-Collard, J.-M.; Frank, M.; Crispin, M.; Coles, J.; Thompson, J.; Ridley, R. A.; Dean, L. S.; Loxham, M.; Azim, A.; Tariq, K.; Johnston, D. A.; Skipp, P. J.; Djukanovic, R.; Baralle, D.; McCormick, C. J.; Davies, D. E.; Lucas, J. S.; Wheway, G.; Mennella, V.

doi:10.1101/2020.07.31.230870

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bioRxiv · 10.1101/2020.07.31.230870

A novel isoform of ACE2 is expressed in human nasal and bronchial respiratory epithelia and is upregulated in response to RNA respiratory virus infection

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Abstract

Angiotensin-converting enzyme 2 (ACE2) is the main entry point in the airways for SARS-CoV-2. ACE2 binding to SARS-CoV-2 protein Spike triggers viral fusion with the cell membrane, resulting in viral RNA genome delivery into the host. Despite ACE2s critical role in SARS-CoV-2 infection, an understanding of ACE2 expression, including in response to viral infection, remains unclear. Until now ACE2 was thought to encode five transcripts and one 805 amino acid protein. Here we identify a novel short isoform of ACE2. Short ACE2 is expressed in the airway epithelium, the main site of SARS-CoV-2 infection; it is substantially upregulated in response to interferon stimulation and RV infection, but not in response to SARS-CoV-2 infection, and it shows differential regulation in asthma patients. This short isoform lacks SARS-CoV-2 spike glycoprotein high-affinity binding sites and altogether, our data are consistent with a model where short ACE2 may influence host susceptibility to SARS-CoV-2 infection.

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Blume, C., Jackson, C. L., Spalluto, C. M., Legebeke, J., Nazlamova, L. A., Conforti, F., Perotin-Collard, J.-M., Frank, M., Crispin, M., Coles, J., Thompson, J., Ridley, R. A., Dean, L. S., Loxham, M., Azim, A., Tariq, K., Johnston, D. A., Skipp, P. J., Djukanovic, R., Baralle, D., McCormick, C. J., Davies, D. E., Lucas, J. S., Wheway, G., Mennella, V.. 2020-07-31. A novel isoform of ACE2 is expressed in human nasal and bronchial respiratory epithelia and is upregulated in response to RNA respiratory virus infection. https://doi.org/10.1101/2020.07.31.230870

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