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
Donnelly Center, 160 College Street, University of Toronto, Toronto, Ontario, Canada, M5S3E1.
Department of Molecular Genetics, 1 King's College Circle, University of Toronto, Toronto, Ontario, Canada, M5S1A8.
Heliyon. 2023 Jan;9(1):e12744. doi: 10.1016/j.heliyon.2022.e12744. Epub 2022 Dec 30.
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 , 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 and . 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 in Calu-3 cells had the strongest impact in preventing SARS-CoV-2 infection when perturbed.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）依靠宿主细胞成分进行感染和复制。确定病毒与宿主的依赖关系为阐明病毒感染和复制所涉及的机制提供了一种有效方法。如果宿主因子依赖关系具有可药用性，那么它可能成为抗病毒治疗的一种有吸引力的策略。在本研究中，我们在非洲绿猴肾细胞（Vero E6）和四种人类细胞系（包括Calu-3、UM-UC-4、人胚肾细胞（HEK-293）和HuH-7）中进行了全基因组CRISPR敲除筛选，以确定SARS-CoV-2感染的基因调节因子。我们的研究结果表明，只有新冠病毒的同源进入受体在所有细胞系中是共同的宿主依赖因子，而其他鉴定出的宿主基因在很大程度上具有细胞系特异性，包括已知的因子和。一些发现的宿主依赖因子集中在细胞信号传导、免疫相关途径和染色质修饰相关的途径上。值得注意的是，在Calu-3细胞中，染色质修饰基因在受到干扰时对预防SARS-CoV-2感染的影响最强。
