Cited by 1,449HIV Research and TreatmentVirus-based gene therapy researchHIV/AIDS drug development and treatment

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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.·2008·Science

DOI 10.1126/science.1152725

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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.

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Host factors exploited by retroviruses
Goff, S. P. (2007) · Nature Reviews Microbiology · doi:10.1038/nrmicro1541 · Cited by 247

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BackgroundInfluential
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N-terminal half of transportin SR2 interacts with HIV integrase
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“Similar discrepancies were observed among screens for HIV host factors (Brass et al., 2008; Konig et al., 2008; Zhou et al., 2008).”
Result

Authors: Brass, A. L., Dykxhoorn, D. M., Benita, Y., Yan, N., Engelman, A., Xavier, R. J., Lieberman, J., & Elledge, S. J.
Affiliations: Brigham and Women's Hospital (US)
ORCID: Dykxhoorn, Derek M.
Benita, Yair
Yan, Nan
Engelman, Alan
Xavier, Ramnik J.
Lieberman, Judy
Elledge, Stephen J.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2008-02-15
Volume: 319
Issue: 5865
Pages: 921-926
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.1152725
OpenAlex: W2145848202
Cited by: 1,449
References: 0
Citations by year: 2026: 12 · 2025: 18 · 2024: 26 · 2023: 28 · 2022: 38 · 2021: 38 · 2020: 52 · 2019: 59 · 2018: 71 · 2017: 53 · 2016: 62 · 2015: 96 · 2014: 90 · 2013: 150 · 2012: 148
FWCI: 57.05
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Funders: Howard Hughes Medical Institute
National Institute of Allergy and Infectious Diseases (U19AI056900, AI052014, AI 062773, R01AI062773, R01AI052014, P30AI060354)
National Institute of Diabetes and Digestive and Kidney Diseases (P30DK040561)
Topics: Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
Keywords: HIV-1, host factors, host-virus interaction, Rab6, viral entry, karyopherins, TNPO3, viral integration, Mediator complex, MED28, viral transcription, antiviral drug targets
MeSH terms: Cytoskeletal Proteins, Humans, Proteins, Transcription, Genetic, Virus Replication, HIV-1, HIV Infections, Virus Integration, Computational Biology, rab GTP-Binding Proteins, Genomics, Karyopherins, Vesicular Transport Proteins, RNA Interference, RNA, Small Interfering, Cell Line, Tumor, Intracellular Signaling Peptides and Proteins, Virus Internalization, Human Immunodeficiency Virus Proteins, Host-Pathogen Interactions, Mediator Complex

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

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