Citation

BibTex format

@article{Ansari:2021:10.12688/wellcomeopenres.16559.1,
author = {Ansari, MA and Marchi, E and Ramamurthy, N and Aschenbrenner, D and Morgan, S and Hackstein, C-P and Lin, S-K and Bowden, R and Sharma, E and Pedergnana, V and Venkateswaran, S and Kugathasan, S and Mo, A and Gibson, G and Cooke, GS and McLauchlan, J and Baillie, JK and Teichmann, S and Mentzer, A and Knight, J and Todd, JA and Hinks, T and Barnes, EJ and Uhlig, HH and Klenerman, P},
doi = {10.12688/wellcomeopenres.16559.1},
journal = {Wellcome Open Research},
pages = {47--47},
title = {In vivo negative regulation of SARS-CoV-2 receptor, ACE2, by interferons and its genetic control},
url = {http://dx.doi.org/10.12688/wellcomeopenres.16559.1},
volume = {6},
year = {2021}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - <ns4:p><ns4:bold>Background</ns4:bold>: Angiotensin I converting enzyme 2 (ACE2) is a receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and differences in its expression may affect susceptibility to infection.</ns4:p><ns4:p> <ns4:bold>Methods</ns4:bold>: We performed a genome-wide expression quantitative trait loci (eQTL) analysis using hepatitis C virus-infected liver tissue from 190 individuals.</ns4:p><ns4:p> <ns4:bold>Results</ns4:bold>: We discovered that polymorphism in a type III interferon gene (<ns4:italic>IFNL4</ns4:italic>), which eliminates IFN-λ4 production, is associated with a two-fold increase in ACE2 RNA expression. Conversely, among genes negatively correlated with <ns4:italic>ACE2 </ns4:italic>expression, IFN-signalling pathways were highly enriched and <ns4:italic>ACE2 </ns4:italic>was downregulated after IFN-α treatment. Negative correlation was also found in the gastrointestinal tract where inflammation driven IFN-stimulated genes were negatively correlated with <ns4:italic>ACE2</ns4:italic> expression and in lung tissue from a murine model of SARS-CoV-1 infection suggesting conserved regulation of <ns4:italic>ACE2 </ns4:italic>across tissue and species.</ns4:p><ns4:p> <ns4:bold>Conclusions</ns4:bold>: We conclude that <ns4:italic>ACE2 </ns4:italic>is likely a negatively-regulated interferon-stimulated gene (ISG) and carriage of <ns4:italic>IFNL4 </ns4:italic>gene alleles which modulates ISGs expression in viral infection may play a role in SARS-CoV-2 pathogenesis with implications for therapeutic interventions.</ns4:p>
AU  - Ansari,MA
AU  - Marchi,E
AU  - Ramamurthy,N
AU  - Aschenbrenner,D
AU  - Morgan,S
AU  - Hackstein,C-P
AU  - Lin,S-K
AU  - Bowden,R
AU  - Sharma,E
AU  - Pedergnana,V
AU  - Venkateswaran,S
AU  - Kugathasan,S
AU  - Mo,A
AU  - Gibson,G
AU  - Cooke,GS
AU  - McLauchlan,J
AU  - Baillie,JK
AU  - Teichmann,S
AU  - Mentzer,A
AU  - Knight,J
AU  - Todd,JA
AU  - Hinks,T
AU  - Barnes,EJ
AU  - Uhlig,HH
AU  - Klenerman,P
DO  - 10.12688/wellcomeopenres.16559.1
EP  - 47
PY  - 2021///
SP  - 47
TI  - In vivo negative regulation of SARS-CoV-2 receptor, ACE2, by interferons and its genetic control
T2  - Wellcome Open Research
UR  - http://dx.doi.org/10.12688/wellcomeopenres.16559.1
UR  - https://doi.org/10.12688/wellcomeopenres.16559.1
VL  - 6
ER  -
Download