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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Chlorocebus sabaeus

PROVIDER: GSE154784 | GEO | 2020/10/05

REPOSITORIES: GEO

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

Project description: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.

| S-EPMC7457610 | biostudies-literature

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

Project description:Identification of host genes essential for SARS-CoV-2 infection may reveal novel therapeutic targets and inform our understanding of COVID-19 pathogenesis. A genome-wide CRISPR screen with SARS-CoV-2 was performed in Vero-E6 cells (data not provided here), identifying 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, the alarmin HMGB1, and the transcription factors Smad3 and Smad4. Small molecule inhibitors of these pathways inhibited SARS-CoV-2-infection in both monkey and human cells, demonstrating the conserved role of these genetic hits across species. We also revealed that HMGB1 is a novel regulator of ACE2 expression and 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.

2020-10-05 | GSE154761 | GEO

Genome-wide CRISPR screen reveals host genes that regulate SARS-CoV-2 infection [RNA-seq]

Project description: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 in Vero-E6 cells, identifying 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, the alarmin HMGB1, and the transcription factors Smad3 and Smad4. Small molecule inhibitors of these pathways inhibited SARS-CoV-2-infection in both monkey and human cells, demonstrating the conserved role of these genetic hits across species. We also revealed that HMGB1 is a novel regulator of ACE2 expression and 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.

2020-10-05 | GSE154783 | GEO

Genome-wide CRISPR screen reveals host genes that regulate SARS-CoV-2 infection [ATAC-seq]

Project description: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 in Vero-E6 cells, identifying 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, the alarmin HMGB1, and the transcription factors Smad3 and Smad4. Small molecule inhibitors of these pathways inhibited SARS-CoV-2-infection in both monkey and human cells, demonstrating the conserved role of these genetic hits across species. We also revealed that HMGB1 is a novel regulator of ACE2 expression and 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.

2020-10-05 | GSE154782 | GEO

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

Project description:Genome-wide CRISPR screen reveals host genes that regulate SARS-CoV-2 infection

| PRJNA647390 | ENA

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

Project description:Genome-wide CRISPR screen reveals host genes that regulate SARS-CoV-2 infection

| PRJNA647422 | ENA

A genome-wide CRISPR screen identifies host factors that regulate SARS-CoV-2 entry.

Project description:The global spread of SARS-CoV-2 is posing major public health challenges. One feature of SARS-CoV-2 spike protein is the insertion of multi-basic residues at the S1/S2 subunit cleavage site. Here, we find that the virus with intact spike (Sfull) preferentially enters cells via fusion at the plasma membrane, whereas a clone (Sdel) with deletion disrupting the multi-basic S1/S2 site utilizes an endosomal entry pathway. Using Sdel as model, we perform a genome-wide CRISPR screen and identify several endosomal entry-specific regulators. Experimental validation of hits from the CRISPR screen shows that host factors regulating the surface expression of angiotensin-converting enzyme 2 (ACE2) affect entry of Sfull virus. Animal-to-animal transmission with the Sdel virus is reduced compared to Sfull in the hamster model. These findings highlight the critical role of the S1/S2 boundary of SARS-CoV-2 spike protein in modulating virus entry and transmission and provide insights into entry of coronaviruses.

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Genome-wide CRISPR screen reveals host genes that regulate SARS-CoV-2 infection [RNA-seq]

Project description:Genome-wide CRISPR screen reveals host genes that regulate SARS-CoV-2 infection [RNA-seq]

| PRJNA647435 | ENA

Genome-wide CRISPR screen reveals host genes that regulate SARS-CoV-2 infection [ATAC-seq]

Project description:Genome-wide CRISPR screen reveals host genes that regulate SARS-CoV-2 infection [ATAC-seq]

| PRJNA647434 | ENA

A CRISPR activation screen identifies genes that enhance SARS-CoV-2 infection

Project description: Not available

| S-EPMC9871949 | biostudies-literature