TY - JOUR
T1 - Genome-Scale RNAi Screen for Host Factors Required for HIV Replication
AU - Zhou, Honglin
AU - Xu, Min
AU - Huang, Qian
AU - Gates, Adam T.
AU - Zhang, Xiaohua D.
AU - Castle, John C.
AU - Stec, Erica
AU - Ferrer, Marc
AU - Strulovici, Berta
AU - Hazuda, Daria J.
AU - Espeseth, Amy S.
PY - 2008/11/13
Y1 - 2008/11/13
N2 - Human immunodeficiency virus (HIV)-1 depends on the host cell machinery to support its replication. To discover cellular factors associated with HIV-1 replication, we conducted a genome-scale siRNA screen, revealing more than 311 host factors, including 267 that were not previously linked to HIV. Surprisingly, there was little overlap between these genes and the HIV dependency factors described recently. However, an analysis of the genes identified in both screens revealed overlaps in several of the associated pathways or protein complexes, including the SP1/mediator complex and the NF-κB signaling pathway. cDNAs for a subset of the identified genes were used to rescue HIV replication following knockdown of the cellular mRNA providing strong evidence that the following six genes are previously uncharacterized host factors for HIV: AKT1, PRKAA1, CD97, NEIL3, BMP2K, and SERPINB6. This study highlights both the power and shortcomings of large scale loss-of-function screens in discovering host-pathogen interactions.
AB - Human immunodeficiency virus (HIV)-1 depends on the host cell machinery to support its replication. To discover cellular factors associated with HIV-1 replication, we conducted a genome-scale siRNA screen, revealing more than 311 host factors, including 267 that were not previously linked to HIV. Surprisingly, there was little overlap between these genes and the HIV dependency factors described recently. However, an analysis of the genes identified in both screens revealed overlaps in several of the associated pathways or protein complexes, including the SP1/mediator complex and the NF-κB signaling pathway. cDNAs for a subset of the identified genes were used to rescue HIV replication following knockdown of the cellular mRNA providing strong evidence that the following six genes are previously uncharacterized host factors for HIV: AKT1, PRKAA1, CD97, NEIL3, BMP2K, and SERPINB6. This study highlights both the power and shortcomings of large scale loss-of-function screens in discovering host-pathogen interactions.
KW - CELLBIO
KW - MICROBIO
KW - SYSBIO
UR - http://www.scopus.com/inward/record.url?scp=55249088255&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=55249088255&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2008.10.004
DO - 10.1016/j.chom.2008.10.004
M3 - Article
C2 - 18976975
AN - SCOPUS:55249088255
SN - 1931-3128
VL - 4
SP - 495
EP - 504
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 5
ER -
