Cited by 544HIV Research and TreatmentHIV/AIDS drug development and treatmentVirus-based gene therapy research

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An Essential Role for LEDGF/p75 in HIV Integration

Llano, Manuel, Saenz, Dyana T., Meehan, Anne, Wongthida, Phonphimon, Peretz, Mary, Walker, William H., Teo, Wulin, Poeschla, Eric M.·2006·Science

DOI 10.1126/science.1132319

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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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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.
ORCID: Saenz, Dyana T.
Meehan, Anne
Wongthida, Phonphimon
Teo, Wulin
Poeschla, Eric M.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2006-10-20
Volume: 314
Issue: 5798
Pages: 461-464
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.1132319
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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An Essential Role for LEDGF/p75 in HIV Integration

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