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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
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Spalluto, Cosma
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Legebeke, Jelmer
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Nazlamova, Liliya
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Conforti, Franco
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Perotin-Collard, 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
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Dean, Lareb
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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
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Skipp, Paul James Stuart
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Djukanovic, Ratko
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Baralle, Diana
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Mccormick, Christopher
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Davies, Donna
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Wheway, Gabrielle
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Mennella, Vito
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Blume, Cornelia
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Jackson, Claire
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Spalluto, Cosma
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Legebeke, Jelmer
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Nazlamova, Liliya
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Conforti, Franco
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Perotin-Collard, 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
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Dean, Lareb
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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
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Skipp, Paul James Stuart
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Djukanovic, Ratko
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Baralle, Diana
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Mccormick, Christopher
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Davies, Donna
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Lucas, Jane
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Wheway, Gabrielle
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Mennella, Vito
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Blume, Cornelia, Jackson, Claire, Spalluto, Cosma, Legebeke, Jelmer, Nazlamova, Liliya, Conforti, Franco, Perotin-Collard, Jeanne-Marie, Frank, Martin, Butler, John, Crispin, Max, Coles, Janice, Thompson, James, Ridley, Robert, Dean, Lareb, Loxham, Matthew, Reikine, Stephanie, Azim, Adnan, Tariq, Kamran, Johnston, David, Skipp, Paul James Stuart, Djukanovic, Ratko, Baralle, Diana, Mccormick, Christopher, Davies, Donna, Lucas, Jane, 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: 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 Max Crispin: ORCID iD orcid.org/0000-0002-1072-2694
ORCID for Matthew Loxham: ORCID iD orcid.org/0000-0001-6459-538X
ORCID for David Johnston: ORCID iD orcid.org/0000-0001-6703-6014
ORCID for Paul James Stuart Skipp: ORCID iD orcid.org/0000-0002-2995-2959
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 Mccormick: ORCID iD orcid.org/0000-0002-6155-9161
ORCID for Donna Davies: ORCID iD orcid.org/0000-0002-5117-2991
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: 26 Nov 2021 05:39

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Contributors

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

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