| Literature DB >> 26190106 |
Hongming Ma1, Ying Dang1, Yonggan Wu2, Gengxiang Jia1, Edgar Anaya1, Junli Zhang1, Sojan Abraham1, Jang-Gi Choi1, Guojun Shi3, Ling Qi3, N Manjunath4, Haoquan Wu5.
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.Entities:
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Year: 2015 PMID: 26190106 PMCID: PMC4559080 DOI: 10.1016/j.celrep.2015.06.049
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423