DOI: 10.1126/science.1152725. Identification of Host Proteins Required for HIV Infection Through a Functional Genomic Screen

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

10.1126/science.1152725

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

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.

Bibliography

Brass, A. L., Dykxhoorn, D. M., Benita, Y., Yan, N., Engelman, A., Xavier, R. J., Lieberman, J., & Elledge, S. J. (2008). Identification of Host Proteins Required for HIV Infection Through a Functional Genomic Screen. Science, 319(5865), 921â926.

Authors 8

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

References 37 Referenced 1,209

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10.1126/science.1143767
We thank the Institute of Chemistry and Cell Biology (ICCB)-Longwood: C. Shamu S. Rudnicki S. Johnston D. Fletcher K. Schulberg and M. Tsui. We also thank F. Diaz-Griffero J. Walsh A. Balazs R. Mulligan R. Sutton V. Ramesh and A. Puri for reagents and guidance; B. Glick G. Hu E. R. McDonald III A. Smorgorzewska N. Solimini M. Krishnan and members of the Elledge lab for help and advice; A. Liao A. Landry and Z. Wu for technical assistance; and E. Golde for facilitating collaborations. Funding for this study was provided by a Crohns and Colitis Foundation of America fellowship (A.L.B.) a Center for Computational and Integrative Biology fellowship (Y.B.) and the Harvard Center for AIDS Research (CFAR) scholar award (N.Y.). J.L. (U19-AI056900) R.J.X. (AI062773) and A.E. (AI052014) are supported by NIH grants. D.M.D. was funded by a grant from the Harvard CFAR to J.L. and S.J.E. S.J.E. is an Investigator with the Howard Hughes Medical Institute.

Dates

Type	When
Created	17 years, 7 months ago (Jan. 10, 2008, 8:59 p.m.)
Deposited	1 year, 7 months ago (Jan. 10, 2024, 4:43 a.m.)
Indexed	1 month, 3 weeks ago (July 3, 2025, 11:10 a.m.)
Issued	17 years, 6 months ago (Feb. 15, 2008)
Published	17 years, 6 months ago (Feb. 15, 2008)
Published Print	17 years, 6 months ago (Feb. 15, 2008)

Funders 0

None

BibTeX

@article{Brass_2008, title={Identification of Host Proteins Required for HIV Infection Through a Functional Genomic Screen}, volume={319}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1152725}, DOI={10.1126/science.1152725}, number={5865}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Brass, Abraham L. and Dykxhoorn, Derek M. and Benita, Yair and Yan, Nan and Engelman, Alan and Xavier, Ramnik J. and Lieberman, Judy and Elledge, Stephen J.}, year={2008}, month=feb, pages={921–926} }

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