In vivo negative regulation of SARS-CoV-2 receptor, ACE2, by interferons and its genetic control

In vivo negative regulation of SARS-CoV-2 receptor, ACE2, by interferons and its genetic control

<br><strong>Background: </strong>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. <br><strong>Methods: </strong>We...

Полное описание

Библиографические подробности
Главные авторы:	Ansari, A, Marchi, E, Ramamurthy, N, Aschenbrenner, D, Morgan, S, Hackstein, C-P, Lin, S-K, Bowden, R, Sharma, E, Pedergnana, V, Venkateswaran, S, Kugathasan, S, Mo, A, Gibson, G, Cooke, G, McLauchlan, J, Baillie, JK, Teichmann, S, Mentzer, A, Knight, J, Todd, J, Hinks, T, Barnes, E, Klenerman, P, Uhlig, H
Другие авторы:	STOP-HCV Consortium
Формат:	Journal article
Язык:	English
Опубликовано:	F1000 Research Ltd 2021

Описание
Итог:	<br><strong>Background: </strong>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. <br><strong>Methods: </strong>We performed a genome-wide expression quantitative trait loci (eQTL) analysis using hepatitis C virus-infected liver tissue from 190 individuals. <br><strong>Results: </strong>We discovered that polymorphism in a type III interferon gene (IFNL4), which eliminates IFN-λ4 production, is associated with a two-fold increase in ACE2 RNA expression. Conversely, among genes negatively correlated with ACE2 expression, IFN-signalling pathways were highly enriched and ACE2 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 ACE2 expression and in lung tissue from a murine model of SARS-CoV-1 infection suggesting conserved regulation of ACE2 across tissue and species. <br><strong>Conclusions: </strong>We conclude that ACE2 is likely a negatively-regulated interferon-stimulated gene (ISG) and carriage of IFNL4 gene alleles which modulates ISGs expression in viral infection may play a role in SARS-CoV-2 pathogenesis with implications for therapeutic interventions.