Survival-based CRISPR genetic screens across a panel of permissive cell lines identify common and cell-specific SARS-CoV-2 host factors

• Published in: Heliyon 2023-01, Vol.9 (1), p.e12744-e12744, Article e12744
• Main Authors: Chan, Katherine, Farias, Adrian Granda, Lee, Hunsang, Guvenc, Furkan, Mero, Patricia, Brown, Kevin R., Ward, Henry, Billmann, Maximilian, Aulakh, Kamaldeep, Astori, Audrey, Haider, Shahan, Marcon, Edyta, Braunschweig, Ulrich, Pu, Shuye, Habsid, Andrea, Yan Tong, Amy Hin, Christie-Holmes, Natasha, Budylowski, Patrick, Ghalami, Ayoob, Mubareka, Samira, Maguire, Finlay, Banerjee, Arinjay, Mossman, Karen L., Greenblatt, Jack, Gray-Owen, Scott D., Raught, Brian, Blencowe, Benjamin J., Taipale, Mikko, Myers, Chad, Moffat, Jason
• Format: Article
• Language: English
• Subjects: ACE2; CRISPR screens; Genome-wide loss-of-function; Host factors; SARS-CoV-2
• ISSN: 2405-8440; 2405-8440
• DOI: 10.1016/j.heliyon.2022.e12744

SARS-CoV-2 depends on host cell components for infection and replication. Identification of virus-host dependencies offers an effective way to elucidate mechanisms involved in viral infection and replication. If druggable, host factor dependencies may present an attractive strategy for anti-viral therapy. In this study, we performed genome wide CRISPR knockout screens in Vero E6 cells and four human cell lines including Calu-3, UM-UC-4, HEK-293 and HuH-7 to identify genetic regulators of SARS-CoV-2 infection. Our findings identified only ACE2, the cognate SARS-CoV-2 entry receptor, as a common host dependency factor across all cell lines, while other host genes identified were largely cell line specific, including known factors TMPRSS2 and CTSL. Several of the discovered host-dependency factors converged on pathways involved in cell signalling, immune-related pathways, and chromatin modification. Notably, the chromatin modifier gene KMT2C in Calu-3 cells had the strongest impact in preventing SARS-CoV-2 infection when perturbed.