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Integrated multi-omics analyses identify key anti-viral host factors and pathways controlling SARS-CoV-2 infection

Host anti-viral factors are essential for controlling SARS-CoV-2 infection but remain largely unknown due to the biases of previous large-scale studies toward pro-viral host factors. To fill in this knowledge gap, we performed a genome-wide CRISPR dropout screen and integrated analyses of the multi-...

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Detalles Bibliográficos
Autores principales: Hou, Jiakai, Wei, Yanjun, Zou, Jing, Jaffery, Roshni, Liang, Shaoheng, Zheng, Caishang, Chen, Ken, Shi, Pei-Yong, Chen, Yiwen, Xie, Xuping, Peng, Weiyi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Journal Experts 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9413708/
https://www.ncbi.nlm.nih.gov/pubmed/36032971
http://dx.doi.org/10.21203/rs.3.rs-1910932/v1
Descripción
Sumario:Host anti-viral factors are essential for controlling SARS-CoV-2 infection but remain largely unknown due to the biases of previous large-scale studies toward pro-viral host factors. To fill in this knowledge gap, we performed a genome-wide CRISPR dropout screen and integrated analyses of the multi-omics data of the CRISPR screen, genome-wide association studies, single-cell RNA-seq, and host-virus proteins or protein/RNA interactome. This study has uncovered many host factors that were missed by previous studies, including the components of V-ATPases, ESCRT, and N-glycosylation pathways that modulated viral entry and/or replication. The cohesin complex was also identified as a novel anti-viral pathway, suggesting an important role of three-dimensional chromatin organization in mediating host-viral interaction. Furthermore, we discovered an anti-viral regulator KLF5, a transcriptional factor involved in sphingolipid metabolism, which was up-regulated and harbored genetic variations linked to the COVID-19 patients with severe symptoms. Our results provide a resource for understanding the host anti-viral network during SARS-CoV-2 infection and may help develop new countermeasure strategies.