title: A CRISPR-Based Screen Identifies Genes Essential for West-Nile-Virus-Induced Cell Death.
abstract: West Nile virus (WNV) causes an acute neurological infection attended by massive neuronal cell death. However, the mechanism(s) behind the virus-induced cell death is poorly understood. Using a library containing 77,406 sgRNAs targeting 20,121 genes, we performed a genome-wide screen followed by a second screen with a sub-library. Among the genes identified, seven genes, EMC2, EMC3, SEL1L, DERL2, UBE2G2, UBE2J1, and HRD1, stood out as having the strongest phenotype, whose knockout conferred strong protection against WNV-induced cell death with two different WNV strains and in three cell lines. Interestingly, knockout of these genes did not block WNV replication. Thus, these appear to be essential genes that link WNV replication to downstream cell death pathway(s). In addition, the fact that all of these genes belong to the ER-associated protein degradation (ERAD) pathway suggests that this might be the primary driver of WNV-induced cell death.
authors.affiliation: Center of Emphasis in Infectious Diseases, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA.
authors.forename: Hongming
authors.initials: H
authors.lastname: Ma
authors.affiliation: Center of Emphasis in Infectious Diseases, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Dang
authors.affiliation: Labii LLC, Mountain View, CA 94043, USA.
authors.forename: Yonggan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Center of Emphasis in Infectious Diseases, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA.
authors.forename: Gengxiang
authors.initials: G
authors.lastname: Jia
authors.affiliation: Center of Emphasis in Infectious Diseases, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA.
authors.forename: Edgar
authors.initials: E
authors.lastname: Anaya
authors.affiliation: Center of Emphasis in Infectious Diseases, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA.
authors.forename: Junli
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Center of Emphasis in Infectious Diseases, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA.
authors.forename: Sojan
authors.initials: S
authors.lastname: Abraham
authors.affiliation: Center of Emphasis in Infectious Diseases, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA.
authors.forename: Jang-Gi
authors.initials: JG
authors.lastname: Choi
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Guojun
authors.initials: G
authors.lastname: Shi
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Qi
authors.affiliation: Center of Emphasis in Infectious Diseases, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA. Electronic address: manjunath.swamy@ttuhsc.edu.
authors.forename: N
authors.initials: N
authors.lastname: Manjunath
authors.affiliation: Center of Emphasis in Infectious Diseases, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA. Electronic address: haoquan.wu@ttuhsc.edu.
authors.forename: Haoquan
authors.initials: H
authors.lastname: Wu
mesh_terms: D064113:CRISPR-Cas Systems; D016923:Cell Death / Q000235:genetics; D060746:Endoplasmic Reticulum-Associated Degradation / Q000235:genetics*; D005796:Genes; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007109:Immunity / Q000235:genetics; D014902:West Nile virus / Q000472:pathogenicity*