The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.
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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“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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Cites
Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein
Sheehy, A. M., Gaddis, N., Choi, J. D., & Malim, M. H. (2002) · Nature · doi:10.1038/nature00939 · Cited by 2,407
HIV-1 Integrase Forms Stable Tetramers and Associates with LEDGF/p75 Protein in Human Cells
Cherepanov, P., Maertens, G., Proost, P., Devreese, B., Van Beeumen, J., Engelborghs, Y., De Clercq, E., & Debyser, Z. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m209278200 · Cited by 704
A role for LEDGF/p75 in targeting HIV DNA integration
Ciuffi, A., Llano, M., Poeschla, E., Hoffmann, C., Leipzig, J., Shinn, P., Ecker, J. R., & Bushman, F. (2005) · Nature Medicine · doi:10.1038/nm1329 · Cited by 658
Self-citationLEDGF/p75 Is Essential for Nuclear and Chromosomal Targeting of HIV-1 Integrase in Human Cells
Maertens, G., Cherepanov, P., Pluymers, W., Busschots, K., De Clercq, E., Debyser, Z., & Engelborghs, Y. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m303594200 · Cited by 493
Llano, M., Vanegas, M., Fregoso, O., Saenz, D., Chung, S., Peretz, M., & Poeschla, E. M. (2004) · Journal of Virology · doi:10.1128/jvi.78.17.9524-9537.2004 · Cited by 305
Self-citationGe, H., Si, Y., & Roeder, R. G. (1998) · The EMBO Journal · doi:10.1093/emboj/17.22.6723 · Cited by 299
Cherepanov, P., Devroe, E., Silver, P. A., & Engelman, A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406307200 · Cited by 287
Solution structure of the HIV-1 integrase-binding domain in LEDGF/p75
Cherepanov, P., Sun, Z.-Y. J., Rahman, S., Maertens, G., Wagner, G., & Engelman, A. (2005) · Nature Structural & Molecular Biology · doi:10.1038/nsmb937 · Cited by 235
Vandekerckhove, L., Christ, F., Maele, B. V., Rijck, J. D., Gijsbers, R., den Haute, C. V., Witvrouw, M., & Debyser, Z. (2006) · Journal of Virology · doi:10.1128/jvi.80.4.1886-1896.2006 · Cited by 210
The Interaction of LEDGF/p75 with Integrase Is Lentivirus-specific and Promotes DNA Binding
Busschots, K., Vercammen, J., Emiliani, S., Benarous, R., Engelborghs, Y., Christ, F., & Debyser, Z. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m411681200 · Cited by 208
Llano, M., Vanegas, M., Hutchins, N., Thompson, D., Delgado, S., & Poeschla, E. M. (2006) · Journal of Molecular Biology · doi:10.1016/j.jmb.2006.04.073 · Cited by 199
Self-citationVanegas, M., Llano, M., Delgado, S., Thompson, D., Peretz, M., & Poeschla, E. M. (2005) · Journal of Cell Science · doi:10.1242/jcs.02299 · Cited by 172
Self-citationLens Epithelium-derived Growth Factor/p75 Prevents Proteasomal Degradation of HIV-1 Integrase
Llano, M., Delgado, S., Vanegas, M., & Poeschla, E. M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m408508200 · Cited by 158
Self-citationVandegraaff, N., Devroe, E., Turlure, F., Silver, P. A., & Engelman, A. (2005) · Virology · doi:10.1016/j.virol.2005.11.022 · Cited by 110
Zielske, S. P., & Stevenson, M. (2006) · Journal of Virology · doi:10.1128/jvi.02470-05 · Cited by 43
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Menin Critically Links MLL Proteins with LEDGF on Cancer-Associated Target Genes
Yokoyama, A., & Cleary, M. L. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.05.003 · Cited by 551
Christ, F., Voet, A., Marchand, A., Nicolet, S., Desimmie, B. A., Marchand, D., Bardiot, D., Van der Veken, N. J., Van Remoortel, B., Strelkov, S. V., et al. (2010) · Nature Chemical Biology · doi:10.1038/nchembio.370 · Cited by 479
Wang, G. P., Ciuffi, A., Leipzig, J., Berry, C. C., & Bushman, F. D. (2007) · Genome Research · doi:10.1101/gr.6286907 · Cited by 457
Shun, M.-C., Raghavendra, N. K., Vandegraaff, N., Daigle, J. E., Hughes, S., Kellam, P., Cherepanov, P., & Engelman, A. (2007) · Genes & Development · doi:10.1101/gad.1565107 · Cited by 467
Host Cell Factors in HIV Replication: Meta-Analysis of Genome-Wide Studies
Bushman, F. D., Malani, N., Fernandes, J. D., D’Orso, I., Cagney, G., Diamond, T. L., Zhou, H., Hazuda, D. J., Espeseth, A. S., König, R., et al. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000437 · Cited by 464
Metadata
- 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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