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

Wei, J.; Alfajaro, M.; Hanna, R.; DeWeirdt, P.; Strine, M.; Lu-Culligan, W.; Zhang, S.-M.; Graziano, V.; Schmitz, C.; Chen, J.; Mankowski, M.; Filler, R.; Gasque, V.; de Miguel, F.; Chen, H.; Oguntuyo, K. Y.; Abriola, L.; Surovtseva, Y.; Orchard, R.; Lee, B.; Lindenbach, B.; Politi, K.; van Dijk, D.; Simon, M.; Yan, Q.; Doench, J. G.; Wilen, C. B.

doi:10.1101/2020.06.16.155101

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bioRxiv · 10.1101/2020.06.16.155101

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

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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-{beta} 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.

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Wei, J., Alfajaro, M., Hanna, R., DeWeirdt, P., Strine, M., Lu-Culligan, W., Zhang, S.-M., Graziano, V., Schmitz, C., Chen, J., Mankowski, M., Filler, R., Gasque, V., de Miguel, F., Chen, H., Oguntuyo, K. Y., Abriola, L., Surovtseva, Y., Orchard, R., Lee, B., Lindenbach, B., Politi, K., van Dijk, D., Simon, M., Yan, Q., Doench, J. G., Wilen, C. B.. 2020-06-17. Genome-wide CRISPR screen reveals host genes that regulate SARS-CoV-2 infection. https://doi.org/10.1101/2020.06.16.155101

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