학술논문

ILRUN Downregulates ACE2 Expression and Blocks Infection of Human Cells by SARS-CoV-2.
Document Type
Article
Source
Journal of Virology. Aug2021, Vol. 95 Issue 15, p1-13. 13p.
Subject
*SARS-CoV-2
*ANGIOTENSIN converting enzyme
*VIRUS diseases
*COVID-19
*TYPE I interferons
*RENIN-angiotensin system
Language
ISSN
0022-538X
Abstract
The human protein-coding gene ILRUN (inflammation and lipid regulator with UBA-like and NBR1-like domains; previously C6orf106) was identified as a proviral factor for Hendra virus infection and was recently characterized to function as an inhibitor of type I interferon expression. Here, we have utilized transcriptome sequencing (RNA-seq) to define cellular pathways regulated by ILRUN in the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of Caco-2 cells. We find that inhibition of ILRUN expression by RNA interference alters transcription profiles of numerous cellular pathways, including upregulation of the SARSCoV-2 entry receptor ACE2 and several other members of the renin-angiotensin aldosterone system. In addition, transcripts of the SARS-CoV-2 coreceptors TMPRSS2 and CTSL were also upregulated. Inhibition of ILRUN also resulted in increased SARS-CoV-2 replication, while overexpression of ILRUN had the opposite effect, identifying ILRUN as a novel antiviral factor for SARS-CoV-2 replication. This represents, to our knowledge, the first report of ILRUN as a regulator of the renin-angiotensin-aldosterone system (RAAS). [ABSTRACT FROM AUTHOR]