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.
|Original language||English (US)|
|State||Published - Jan 2023|
Bibliographical noteFunding Information:
We would like to acknowledge Anne-Claude Gingras and Payman Samavarchi-Tehrani for sharing HEK-293 +A+T cell line and Betty Poon for assistance in the C-CL3 facility. This work was supported by the University of Toronto COVID-19 Action Initiative Fund to J.M., B.J.B., S.G.O., J.G., K.M., and S.M. Indirect support was also received from the University of Toronto and the Temerty Foundation to support enhanced capacity and operations of the Toronto Combined Containment Level 3 Facility during the COVID-19 pandemic. This work was also partially supported from a Canadian Institutes for Health Research Project Grant to J.M. ( MOP142375 ) and a Disruptive Innovations Phase 2 Grant from Genome Canada to J.M.
© 2023 The Authors
- CRISPR screens
- Genome-wide loss-of-function
- Host factors