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Published Online January 10, 2008
Science DOI: 10.1126/science.1152725

Research Articles

Submitted on November 7, 2007
Accepted on December 21, 2007

Identification of Host Proteins Required for HIV Infection Through a Functional Genomic Screen

Abraham L. Brass 1, Derek M. Dykxhoorn 2{dagger}, Yair Benita 3{dagger}, Nan Yan 2, Alan Engelman 4, Ramnik J. Xavier 5, Judy Lieberman 2, Stephen J. Elledge 6*

1 Department of Genetics, Center for Genetics and Genomics, Brigham and Women’s Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.; Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
2 Immune Disease Institute and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
3 Center for Computational and Integrative Biology, Harvard Medical School, Boston, MA 02114, USA.
4 Dana-Farber Cancer Institute, Division of AIDS, Harvard Medical School, Boston, MA 02115, USA.
5 Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.; Center for Computational and Integrative Biology, Harvard Medical School, Boston, MA 02114, USA.
6 Department of Genetics, Center for Genetics and Genomics, Brigham and Women’s Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.

* To whom correspondence should be addressed.
Stephen J. Elledge , E-mail: selledge{at}genetics.med.harvard.edu

{dagger}These authors contributed equally to this work.

HIV-1 exploits multiple host proteins during infection. We performed a large-scale siRNA screen to identify host factors required by HIV-1 and identified over 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.


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