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Identification of Host Proteins Required for HIV Infection Through a Functional Genomic Screen
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 proteins with potential functions in the viral lifecycle have also been identified using siRNA-based screens (125-127).”
From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [127]
In the citing paper
“| Mixed pattern of regulation upon HIV-1 infection | GlyRS | 127 |”
From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [127]
In the citing paper
“The five ARSs listed exhibit a significant decrease (Ն16-fold) in transcript levels.”
From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [127]
In the citing paper
“| Levels of transcripts decrease upon HIV-1 infection b | EPRS a , TyrRS, MetRS a , HisRS, PheRS | 127 |”
From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [127]
In the citing paper
“| Levels of transcripts increase upon HIV-1 infection | AsnRS, CysRS | 127 |”
From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [127]
In the citing paper
“Five other ARSs, AlaRS, IleRS, LysRS, ValRS, and GlnRS, exhibit a moderate decrease (ϳ4fold) in HIV-1-infected cells.”
From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [127]
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Host factors exploited by retroviruses
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Metadata
- 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
- Venue
- Science
- Published
- 2008-02-15
- Volume
- 319
- Issue
- 5865
- Pages
- 921-926
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- 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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