Genome-wide CRISPR screen reveals host genes that regulate SARS-CoV-2 infection.
Jin WeiMia Madel AlfajaroRuth E HannaPeter C DeWeirdtMadison S StrineWilliam J Lu-CulliganShang-Min ZhangVincent R GrazianoCameron O SchmitzJennifer S ChenMadeleine C MankowskiRenata B FillerVictor GasqueFernando de MiguelHuacui ChenKasopefoluwa OguntuyoLaura AbriolaYulia V SurovtsevaRobert C OrchardBenhur LeeBrett LindenbachKaterina PolitiDavid van DijkMatthew D SimonQin YanJohn G DoenchCraig B WilenPublished in: bioRxiv : the preprint server for biology (2020)
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.
Keyphrases
- sars cov
- genome wide
- respiratory syndrome coronavirus
- dna methylation
- small molecule
- copy number
- cell death
- signaling pathway
- induced apoptosis
- cell cycle arrest
- high glucose
- high throughput
- gene expression
- magnetic resonance
- coronavirus disease
- drug induced
- magnetic resonance imaging
- epithelial mesenchymal transition
- risk assessment
- cell proliferation
- endoplasmic reticulum stress
- angiotensin ii
- transforming growth factor
- crispr cas
- anti inflammatory