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

被引：118

作者：

Blume, Cornelia ^{[1
,2
,3
]}

Jackson, Claire L. ^{[1
,2
,3
,4
]}

Spalluto, Cosma Mirella ^{[1
,5
,6
]}

Legebeke, Jelmer ^{[7
]}

Nazlamova, Liliya ^{[1
]}

Conforti, Franco ^{[1
,2
,3
]}

Perotin, Jeanne-Marie ^{[2
,3
,8
]}

Frank, Martin ^{[9
]}

Butler, John ^{[10
]}

Crispin, Max ^{[4
,10
]}

Coles, Janice ^{[1
,2
,3
]}

Thompson, James ^{[1
,2
,3
]}

Ridley, Robert A. ^{[1
,2
,3
]}

Dean, Lareb S. N. ^{[1
,2
,3
]}

Loxham, Matthew ^{[1
,2
,3
,4
]}

Reikine, Stephanie ^{[11
]}

Azim, Adnan ^{[1
,2
,3
]}

Tariq, Kamran ^{[1
,2
,3
]}

Johnston, David A. ^{[1
,12
]}

Skipp, Paul J. ^{[4
,10
]}

Djukanovic, Ratko ^{[1
,2
,3
]}

Baralle, Diana ^{[2
,3
,7
]}

McCormick, Christopher J. ^{[1
,2
,3
]}

Davies, Donna E. ^{[1
,2
,3
,4
]}

Lucas, Jane S. ^{[1
,2
,3
,4
]}

Wheway, Gabrielle ^{[4
,7
]}

Mennella, Vito ^{[1
,2
,3
,4
]}

机构：

[1] Univ Southampton, Fac Med, Sch Clin & Expt Sci, Southampton, Hants, England

[2] Univ Southampton, Southampton NIHR Biomed Res Ctr, Southampton, Hants, England

[3] Univ Hosp Southampton NHS Fdn Trust, Southampton, Hants, England

[4] Univ Southampton, Inst Life Sci, Southampton, Hants, England

[5] Univ Southampton, Fac Med, Southampton, Hants, England

[6] Wessex Invest Sci Hub, Southampton, Hants, England

[7] Univ Southampton, Fac Med, Sch Human Dev & Hlth, Southampton, Hants, England

[8] Univ Hosp, Dept Resp Dis, UMRS1250, Reims, France

[9] Biognos AB, Gothenburg, Sweden

[10] Univ Southampton, Fac Environm & Life Sci, Sch Biol Sci, Southampton, Hants, England

[11] Nuclera Nucle Ltd, Cambridge, England

[12] Univ Southampton, Fac Med, Biomed Imaging Unit, Southampton, Hants, England

来源：

NATURE GENETICS | 2021年 / 53卷 / 02期

基金：

英国惠康基金; 英国生物技术与生命科学研究理事会;

关键词：

ANGIOTENSIN-CONVERTING ENZYME; SYNDROME CORONAVIRUS INFECTION; CELL LINE; SARS-COV-2; SARS; IDENTIFICATION; RECEPTOR; ASTHMA; ENTRY; DIFFERENTIATION;

D O I：

10.1038/s41588-020-00759-x

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：205 / +

页数：26

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