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

A novel ACE2 isoform is expressed in human respiratory epithelia and is upregulated in response to interferons and RNA respiratory virus infection
A novel ACE2 isoform is expressed in human respiratory epithelia and is upregulated in response to interferons and RNA respiratory virus infection
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.
1061-4036
205-214
Blume, Cornelia
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Jackson, Claire L.
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Spalluto, Cosma Mirella
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Legebeke, Jelmer
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Nazlamova, Liliya
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Conforti, Franco
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Perotin, Jeanne Marie
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Frank, Martin
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Butler, John
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Crispin, Max
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Coles, Janice
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Thompson, James
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Ridley, Robert A.
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Dean, Lareb S.N.
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Loxham, Matthew
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Reikine, Stephanie
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Azim, Adnan
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Tariq, Kamran
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Johnston, David A.
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Skipp, Paul J.
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Djukanovic, Ratko
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Baralle, Diana
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McCormick, Christopher J.
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Davies, Donna E.
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Lucas, Jane S.
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Wheway, Gabrielle
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Mennella, Vito
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Blume, Cornelia
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Jackson, Claire L.
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Spalluto, Cosma Mirella
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Legebeke, Jelmer
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Nazlamova, Liliya
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Conforti, Franco
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Perotin, Jeanne Marie
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Frank, Martin
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Butler, John
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Crispin, Max
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Coles, Janice
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Thompson, James
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Ridley, Robert A.
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Dean, Lareb S.N.
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Loxham, Matthew
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Reikine, Stephanie
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Azim, Adnan
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Tariq, Kamran
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Johnston, David A.
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Skipp, Paul J.
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Djukanovic, Ratko
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Baralle, Diana
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McCormick, Christopher J.
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Davies, Donna E.
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Lucas, Jane S.
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Wheway, Gabrielle
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Mennella, Vito
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Blume, Cornelia, Jackson, Claire L., Spalluto, Cosma Mirella, Legebeke, Jelmer, Nazlamova, Liliya, Conforti, Franco, Perotin, Jeanne Marie, Frank, Martin, Butler, John, Crispin, Max, Coles, Janice, Thompson, James, Ridley, Robert A., Dean, Lareb S.N., Loxham, Matthew, Reikine, Stephanie, Azim, Adnan, Tariq, Kamran, Johnston, David A., Skipp, Paul J., Djukanovic, Ratko, Baralle, Diana, McCormick, Christopher J., Davies, Donna E., Lucas, Jane S., Wheway, Gabrielle and Mennella, Vito (2021) A novel ACE2 isoform is expressed in human respiratory epithelia and is upregulated in response to interferons and RNA respiratory virus infection. Nature Genetics, 53 (2), 205-214. (doi:10.1101/2020.07.31.230870).

Record type: Article

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.

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SUBMITTED_58504_2_merged_1604666558 - Accepted Manuscript
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Accepted/In Press date: 1 December 2020
e-pub ahead of print date: 11 January 2021
Published date: 1 February 2021

Identifiers

Local EPrints ID: 445899
URI: http://eprints.soton.ac.uk/id/eprint/445899
ISSN: 1061-4036
PURE UUID: eaee857a-eb58-461f-81ba-c851e796595b
ORCID for Cornelia Blume: ORCID iD orcid.org/0000-0001-6133-7318
ORCID for Claire L. Jackson: ORCID iD orcid.org/0000-0002-1200-0935
ORCID for Cosma Mirella Spalluto: ORCID iD orcid.org/0000-0001-7273-0844
ORCID for Jelmer Legebeke: ORCID iD orcid.org/0000-0003-1194-8959
ORCID for Max Crispin: ORCID iD orcid.org/0000-0002-1072-2694
ORCID for Lareb S.N. Dean: ORCID iD orcid.org/0000-0002-8703-9236
ORCID for David A. Johnston: ORCID iD orcid.org/0000-0001-6703-6014
ORCID for Ratko Djukanovic: ORCID iD orcid.org/0000-0001-6039-5612
ORCID for Diana Baralle: ORCID iD orcid.org/0000-0003-3217-4833
ORCID for Christopher J. McCormick: ORCID iD orcid.org/0000-0002-6155-9161
ORCID for Donna E. Davies: ORCID iD orcid.org/0000-0002-5117-2991
ORCID for Jane S. Lucas: ORCID iD orcid.org/0000-0001-8701-9975
ORCID for Gabrielle Wheway: ORCID iD orcid.org/0000-0002-0494-0783
ORCID for Vito Mennella: ORCID iD orcid.org/0000-0002-4842-9012

Catalogue record

Date deposited: 13 Jan 2021 17:31
Last modified: 17 Mar 2024 06:04

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Contributors

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

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