Genome-scale RNAi screen for host factors required for HIV replication.
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-kappaB 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.
Zhou
Honglin
H
Department of Virus and Cell Biology, Merck & Co., Inc., West Point, PA 19486, USA.
Xu
Min
M
Huang
Qian
Q
Gates
Adam T
AT
Zhang
Xiaohua D
XD
Castle
John C
JC
Stec
Erica
E
Ferrer
Marc
M
Strulovici
Berta
B
Hazuda
Daria J
DJ
Espeseth
Amy S
AS
D016678:Genome; D015658:HIV Infections / Q000235:genetics* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D034622:RNA Interference; D014779:Virus Replication