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

被引：194

作者：

Ma, Hongming ^{[1
]}

Dang, Ying ^{[1
]}

Wu, Yonggan ^{[2
]}

Jia, Gengxiang ^{[1
]}

Anaya, Edgar ^{[1
]}

Zhang, Junli ^{[1
]}

Abraham, Sojan ^{[1
]}

Choi, Jang-Gi ^{[1
]}

Shi, Guojun ^{[3
]}

Qi, Ling ^{[3
]}

Manjunath, N. ^{[1
]}

Wu, Haoquan ^{[1
]}

机构：

[1] Texas Tech Univ, Hlth Sci Ctr, Paul L Foster Sch Med, Ctr Emphasis Infect Dis,Dept Biomed Sci, El Paso, TX 79905 USA

[2] Labii LLC, Mountain View, CA 94043 USA

[3] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA

来源：

CELL REPORTS | 2015年 / 12卷 / 04期

关键词：

RETICULUM-ASSOCIATED DEGRADATION; ENDOPLASMIC-RETICULUM; ENCEPHALITIS-VIRUS; HOST FACTORS; CAS SYSTEMS; GENOME; INFECTION; REPLICATION; ENDONUCLEASE; ACTIVATION;

D O I：

10.1016/j.celrep.2015.06.049

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：673 / 683

页数：11

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