학술논문
Survival-based CRISPR genetic screens across a panel of permissive cell lines identify common and cell-specific SARS-CoV-2 host factors
Document Type
article
Author
Katherine Chan; Adrian Granda Farias; Hunsang Lee; Furkan Guvenc; Patricia Mero; Kevin R. Brown; Henry Ward; Maximilian Billmann; Kamaldeep Aulakh; Audrey Astori; Shahan Haider; Edyta Marcon; Ulrich Braunschweig; Shuye Pu; Andrea Habsid; Amy Hin Yan Tong; Natasha Christie-Holmes; Patrick Budylowski; Ayoob Ghalami; Samira Mubareka; Finlay Maguire; Arinjay Banerjee; Karen L. Mossman; Jack Greenblatt; Scott D. Gray-Owen; Brian Raught; Benjamin J. Blencowe; Mikko Taipale; Chad Myers; Jason Moffat
Source
Heliyon, Vol 9, Iss 1, Pp e12744- (2023)
Subject
Language
English
ISSN
2405-8440
Abstract
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.