Genome-Scale RNAi Screen for Host Factors Required for HIV Replication

Honglin Zhou, Min Xu, Qian Huang, Adam T. Gates, Xiaohua D. Zhang, John C. Castle, Erica Stec, Marc Ferrer, Berta Strulovici, Daria J. Hazuda, Amy S. Espeseth

Research output: Contribution to journalArticlepeer-review

615 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)495-504
Number of pages10
JournalCell Host and Microbe
Volume4
Issue number5
DOIs
StatePublished - Nov 13 2008

Keywords

  • CELLBIO
  • MICROBIO
  • SYSBIO

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

Fingerprint

Dive into the research topics of 'Genome-Scale RNAi Screen for Host Factors Required for HIV Replication'. Together they form a unique fingerprint.

Cite this