Genome-wide CRISPR screen reveals host genes that regulate SARS-CoV-2 infection.

BioRxiv : the Preprint Server for Biology
Jin WeiCraig B Wilen

Abstract

Identification of host genes essential for SARS-CoV-2 infection may reveal novel therapeutic targets and inform our understanding of COVID-19 pathogenesis. Here we performed a genome-wide CRISPR screen with SARS-CoV-2 and identified known SARS-CoV-2 host factors including the receptor ACE2 and protease Cathepsin L. We additionally discovered novel pro-viral genes and pathways including the SWI/SNF chromatin remodeling complex and key components of the TGF-β signaling pathway. Small molecule inhibitors of these pathways prevented SARS-CoV-2-induced cell death. We also revealed that the alarmin HMGB1 is critical for SARS-CoV-2 replication. In contrast, loss of the histone H3.3 chaperone complex sensitized cells to virus-induced death. Together this study reveals potential therapeutic targets for SARS-CoV-2 and highlights host genes that may regulate COVID-19 pathogenesis.

Citations

Sep 24, 2020·Scientific Data·Scott A OchsnerNeil J McKenna
Jul 12, 2020·Nature Reviews. Immunology·Fangfang Lu, Michael Tellier
Oct 25, 2020·Viruses·Karsten KreyAndreas Pichlmair
Oct 19, 2020·Protein Science : a Publication of the Protein Society·Rose OughtredMike Tyers
Aug 14, 2020·The Journal of Cell Biology·Fred D MastJohn D Aitchison
Dec 20, 2020·Scientific Reports·Nicholas ParkinsonSara Clohisey
Dec 12, 2020·Nature·Erola Pairo-CastineiraJ Kenneth Baillie
Apr 24, 2021·ELife·David W SandersClifford P Brangwynne

Methods Mentioned

BETA
PCR
nuclear translocation

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