ILRUN Downregulates ACE2 Expression and Blocks Infection of Human Cells by SARS-CoV-2

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• The gene ILRUN (inflammation and lipid regulator) was previously linked to Hendra virus and inhibits type I interferon.
• Understanding host-virus interactions is crucial for developing therapies against emerging infectious diseases like SARS-CoV-2.

Purpose of the Study:

• To define cellular pathways regulated by ILRUN during SARS-CoV-2 infection.
• To investigate ILRUN's role as a potential antiviral factor against SARS-CoV-2.

Main Methods:

• Transcriptome sequencing (RNA-seq) was used to analyze gene expression changes in Caco-2 cells with altered ILRUN levels during SARS-CoV-2 infection.
• RNA interference was employed to inhibit ILRUN expression, and its overexpression was also studied.

Main Results:

• Inhibition of ILRUN led to the upregulation of SARS-CoV-2 entry receptors ACE2, TMPRSS2, and CTSL.
• ILRUN inhibition resulted in increased SARS-CoV-2 replication, while ILRUN overexpression decreased it.
• ILRUN was identified as a novel regulator of the renin-angiotensin-aldosterone system (RAAS).

Conclusions:

• ILRUN functions as a novel antiviral factor against SARS-CoV-2.
• ILRUN's antiviral activity is mediated, in part, by regulating the expression of key SARS-CoV-2 entry receptors.
• These findings provide insights into host-pathogen interactions and potential therapeutic strategies for COVID-19.