TY - JOUR
T1 - A CRISPR-based screen identifies genes essential for west-nile-virus-induced cell death
AU - Ma, Hongming
AU - Dang, Ying
AU - Wu, Yonggan
AU - Jia, Gengxiang
AU - Anaya, Edgar
AU - Zhang, Junli
AU - Abraham, Sojan
AU - Choi, Jang Gi
AU - Shi, Guojun
AU - Qi, Ling
AU - Manjunath, N.
AU - Wu, Haoquan
N1 - Publisher Copyright:
© 2015 The Authors.
PY - 2015
Y1 - 2015
N2 - West Nile virus (WNV) causes an acute neurological infection attended by massive neuronal cell death. However, the mechanism(s) behind the virusinduced 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 WNVinduced 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.
AB - West Nile virus (WNV) causes an acute neurological infection attended by massive neuronal cell death. However, the mechanism(s) behind the virusinduced 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 WNVinduced 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.
UR - http://www.scopus.com/inward/record.url?scp=84947048286&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2015.06.049
DO - 10.1016/j.celrep.2015.06.049
M3 - Article
C2 - 26190106
AN - SCOPUS:84947048286
SN - 2211-1247
VL - 12
SP - 673
EP - 683
JO - Cell Reports
JF - Cell Reports
IS - 4
ER -