Identification of host proteins required for HIV infection through a functional genomic screen

Abraham L. Brass, Derek M. Dykxhoorn, Yair Benita, Nan Yan, Alan Engelman, Ramnik J. Xavier, Judy Lieberman, Stephen J. Elledge

Research output: Contribution to journalArticle

1042 Citations (Scopus)

Abstract

HIV-1 exploits multiple host proteins during infection. We performed a large-scale small interfering RNA screen to identify host factors required by HIV-1 and identified more than 250 HIV-dependency factors (HDFs). These proteins participate in a broad array of cellular functions and implicate new pathways in the viral life cycle. Further analysis revealed previously unknown roles for retrograde Golgi transport proteins (Rab6 and Vps53) in viral entry, a karyopherin (TNPO3) in viral integration, and the Mediator complex (Med28) in viral transcription. Transcriptional analysis revealed that HDF genes were enriched for high expression in immune cells, suggesting that viruses evolve in host cells that optimally perform the functions required for their life cycle. This effort illustrates the power with which RNA interference and forward genetics can be used to expose the dependencies of human pathogens such as HIV, and in so doing identify potential targets for therapy.

Original languageEnglish (US)
Pages (from-to)921-926
Number of pages6
JournalScience
Volume319
Issue number5865
DOIs
StatePublished - Feb 15 2008

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HIV Infections
HIV
Life Cycle Stages
HIV-1
Mediator Complex
Karyopherins
Virus Integration
Proteins
RNA Interference
Small Interfering RNA
Carrier Proteins
Viruses
Infection
Genes
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Brass, A. L., Dykxhoorn, D. M., Benita, Y., Yan, N., Engelman, A., Xavier, R. J., ... Elledge, S. J. (2008). Identification of host proteins required for HIV infection through a functional genomic screen. Science, 319(5865), 921-926. https://doi.org/10.1126/science.1152725

Identification of host proteins required for HIV infection through a functional genomic screen. / Brass, Abraham L.; Dykxhoorn, Derek M.; Benita, Yair; Yan, Nan; Engelman, Alan; Xavier, Ramnik J.; Lieberman, Judy; Elledge, Stephen J.

In: Science, Vol. 319, No. 5865, 15.02.2008, p. 921-926.

Research output: Contribution to journalArticle

Brass, AL, Dykxhoorn, DM, Benita, Y, Yan, N, Engelman, A, Xavier, RJ, Lieberman, J & Elledge, SJ 2008, 'Identification of host proteins required for HIV infection through a functional genomic screen', Science, vol. 319, no. 5865, pp. 921-926. https://doi.org/10.1126/science.1152725
Brass AL, Dykxhoorn DM, Benita Y, Yan N, Engelman A, Xavier RJ et al. Identification of host proteins required for HIV infection through a functional genomic screen. Science. 2008 Feb 15;319(5865):921-926. https://doi.org/10.1126/science.1152725
Brass, Abraham L. ; Dykxhoorn, Derek M. ; Benita, Yair ; Yan, Nan ; Engelman, Alan ; Xavier, Ramnik J. ; Lieberman, Judy ; Elledge, Stephen J. / Identification of host proteins required for HIV infection through a functional genomic screen. In: Science. 2008 ; Vol. 319, No. 5865. pp. 921-926.
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