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Cell Rep. 2015 Jul 28;12(4):673-83. doi: 10.1016/j.celrep.2015.06.049. Epub 2015 Jul 16.

A CRISPR-Based Screen Identifies Genes Essential for West-Nile-Virus-Induced Cell Death.

Author information

1
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.
2
Labii LLC, Mountain View, CA 94043, USA.
3
Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.
4
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.
5
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.

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.

PMID:
26190106
PMCID:
PMC4559080
DOI:
10.1016/j.celrep.2015.06.049
[Indexed for MEDLINE]
Free PMC Article

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