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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

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    ILRUN downregulates ACE2 HGNC expression and blocks infection of human cells by SARS-CoV-2

    Authors: Leon Tribolet; Marina Alexander; Aaron Brice; Petrus Jansen Van Vuren; Christina Rootes; Kostlend Mara; Meg McDonald; Kerri Bruce; Tamara Gough; Shuning Shi; Christopher Cowled; Andrew Bean; Cameron R. Stewart

    doi:10.1101/2020.11.13.381343 Date: 2020-11-13 Source: bioRxiv

    The human protein-coding gene ILRUN ( inflammation MESHD and lipid regulator with UBA-like and NBR1-like domain, previously C6orf106 HGNC) is a recently-characterised inhibitor of the transcription regulators p300 HGNC and CREB-binding protein HGNC ( CBP HGNC). Here we have utilised RNA-seq to define cellular pathways regulated by ILRUN in the context of severe acute respiratory syndrome MESHD-associated coronavirus-2 ( SARS-CoV-2) infection MESHD. We find that inhibition of ILRUN expression increases cellular expression of several members of the renin-angiotensin aldosterone system (RAAS), including the SARS-CoV-2 entry receptor angiotensin converting enzyme 2 ( ACE2 HGNC). Furthermore, inhibition of ILRUN results in increased SARS-CoV-2 replication. These data identify ILRUN as a novel inhibitor of SARS-CoV-2 replication and represents, to our knowledge, the first report of ILRUN as a regulator of the RAAS. SIGNIFICANCE STATEMENTThere is no doubt that the current rapid global spread of COVID-19 MESHD has had significant and far-reaching impacts on our health and economy and will continue to do so. Research in emerging infectious diseases, such as severe acute respiratory syndrome-associated coronavirus (SARS-CoV-2), is growing rapidly, with new breakthroughs in the understanding of host-virus interactions and the development of innovative and exciting therapeutic strategies and new knowledge and tools to better protect against the impacts of disease. The human protein-coding gene ILRUN is a recently-characterised inhibitor of the transcription regulators p300 HGNC and CREB-binding protein HGNC ( CBP HGNC). Here we present the first evidence that ILRUN modulation has implications for SARS-CoV-2 infection MESHDs. Virus infectivity assays confirmed that gene silencing of ILRUN had a proviral effect and increased SARS-CoV-2 replication, whilst over-expression of ILRUN inhibited SARS-CoV-2 production. Additionally, we observed that ILRUN also regulates the expression of key elements of the RAAS. These data have important implications for the development of antiviral strategies to deal with the current SARS-CoV-2 pandemic.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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