An essential role for LEDGF/p75 in HIV integration
Abstract
Chromosomal integration enables human immunodeficiency virus (HIV) to establish a permanent reservoir that can be therapeutically suppressed but not eradicated. Participation of cellular proteins in this obligate replication step is poorly understood. We used intensified RNA interference and dominant-negative protein approaches to show that the cellular transcriptional coactivator lens epithelium–derived growth factor (LEDGF)/p75 (p75) is an essential HIV integration cofactor. The mechanism requires both linkages of a molecular tether that p75 forms between integrase and chromatin. Fractionally minute levels of endogenous p75 are sufficient to enable integration, showing that cellular factors that engage HIV after entry may elude identification in less intensive knockdowns. Perturbing the p75-integrase interaction may have therapeutic potential.
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LEDGF/p75 is critical but not strictly essential for HIV-1 integration and replication.
“However, while LEDGF/p75 is critical, it is not strictly essential for HIV-1 integration and replication. This assertion is supported by the fact that HIV-1 was able to replicate, albeit at a much-reduced level, in LEDGF knockdown cells, and the replication could be restored upon expression of LEDGF/p75 (Llano et al. 2006, Shun et al. 2007).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Llano et al. 2006
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Self-citation
- Authors
- Llano, M., Saenz, D. T., Meehan, A., Wongthida, P., Peretz, M., Walker, W. H., Teo, W., & Poeschla, E. M.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Poeschla, Eric M.
- Venue
- Science
- Published
- 2006-10-20
- Volume
- 314
- Issue
- 5798
- Pages
- 461-464
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2085489729
- Cited by
- 537
- References
- 15
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 15 · 2023: 10 · 2022: 22 · 2021: 21 · 2020: 16 · 2019: 22 · 2018: 18 · 2017: 22 · 2016: 27 · 2015: 28 · 2014: 43 · 2013: 30 · 2012: 45
- FWCI
- 13.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Keywords
- LEDGF/p75, HIV integration, HIV integrase, chromosomal integration, transcriptional coactivator, HIV reservoir, RNAi knockdown, dominant negative protein
- MeSH terms
- Cell Line, Chromatin, Humans, Recombinant Fusion Proteins, Transcription Factors, Virus Replication, CD4-Positive T-Lymphocytes, HIV-1, Virus Integration, HIV Integrase, RNA Interference, Intercellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing
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