ArticleJournal of virology2006
Transient and stable knockdown of the integrase cofactor LEDGF/p75 reveals its role in the replication cycle of human immunodeficiency virus.
Article in Journal of virology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers, 1 of them a synthesis that pooled it.
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Who cites it
119 citing papers in PubMed, 1 synthesis or guideline pooled it, 209 citations in OpenAlex.
- Specialized DNA Structures Act as Genomic Beacons for Integration by Evolutionarily Diverse Retroviruses.Viruses · 2023Pooled it
- Absence of Ledgf in mouse brain affects the Kmt2a/b and polycomb balance, synaptic transmission and motor function.Acta neuropathologica communications · 2026Article
- Early pandemic HIV-1 integration site preferences differ across anatomical sites.Communications medicine · 2025Article
- BRD4 modulator ZL0580 and LEDGINs additively block and lock HIV-1 transcription.Nature communications · 2025Article
- KuINins as a New Class of HIV-1 Inhibitors That Block Post-Integration DNA Repair.International journal of molecular sciences · 2023Article
- Review
- Complex Relationships between HIV-1 Integrase and Its Cellular Partners.International journal of molecular sciences · 2022Review
- Delivering genes with human immunodeficiency virus-derived vehicles: still state-of-the-art after 25 years.Journal of biomedical science · 2022Review
- HIV-1 Preintegration Complex Preferentially Integrates the Viral DNA into Nucleosomes Containing Trimethylated Histone 3-Lysine 36 Modification and Flanking Linker DNA.Journal of virology · 2022Article
- Multivalent interactions essential for lentiviral integrase function.Nature communications · 2022Article
- Article
- Towards a Functional Cure of HIV-1: Insight Into the Chromatin Landscape of the Provirus.Frontiers in microbiology · 2021Review
- LEDGINs, Inhibitors of the Interaction Between HIV-1 Integrase and LEDGF/p75, Are Potent Antivirals with a Potential to Cure HIV Infection.Advances in experimental medicine and biology · 2021Article
- Strategies for Targeting Retroviral Integration for Safer Gene Therapy: Advances and Challenges.Frontiers in molecular biosciences · 2021Review
- HIV-1 Maturation: Lessons Learned from Inhibitors.Viruses · 2020Review
- Reduce and Control: A Combinatorial Strategy for Achieving Sustained HIV Remissions in the Absence of Antiretroviral Therapy.Viruses · 2020Review
- Twenty years of research on the DFS70/LEDGF autoantibody-autoantigen system: many lessons learned but still many questions.Auto- immunity highlights · 2020Review
- Multifaceted HIV integrase functionalities and therapeutic strategies for their inhibition.The Journal of biological chemistry · 2019Review
- TGF-β1 increases viral burden and promotes HIV-1 latency in primary differentiated human bronchial epithelial cells.Scientific reports · 2019Article
- Interaction of HIV-1 integrase with polypyrimidine tract binding protein and associated splicing factor (PSF) and its impact on HIV-1 replication.Retrovirology · 2019Article
59 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
After identifying the interaction between the transcriptional coactivator lens epithelium-derived growth factor (LEDGF/p75) and the human immunodeficiency virus type 1 (HIV-1) integrase (IN), we have now investigated the role of LEDGF/p75 during HIV replication. Transient small interfering RNA-mediated knockdown of LEDGF/p75 in HeLaP4 cells resulted in a three- to fivefold inhibition of HIV-1 (strain NL4.3) replication. Quantitative PCR was used to pinpoint the replication block to the integration step. Next, polyclonal and monoclonal HeLaP4-derived cell lines were selected with a stable knockdown of LEDGF/p75 mediated by a lentiviral vector (lentivector) encoding a short hairpin RNA (shRNA) targeting this protein. Cell lines stably transduced with a lentivector encoding an unrelated hairpin or a double-mismatch hairpin served as controls. Again, a two- to fourfold reduction of HIV-1 replication was observed. The extent of LEDGF/p75 knockdown closely correlated with the reduction of HIV-1 replication. After the back-complementation of LEDGF/p75 in the poly- and monoclonal knockdown cell lines using an shRNA-resistant expression plasmid, viral replication was restored to nearly wild-type levels. The Q168A mutation in integrase has been shown to interfere with the interaction with LEDGF/p75 without reducing the enzymatic activity. Transduction by HIV-1-derived lentivectors carrying the Q168A IN mutant was severely hampered, pointing again to a requirement for LEDGF/p75. Altogether, our data validate LEDGF/p75 as an important cellular cofactor for HIV integration and as a potential target for antiviral drug development.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.