ArticleEBioMedicine2016
LEDGIN-mediated Inhibition of Integrase-LEDGF/p75 Interaction Reduces Reactivation of Residual Latent HIV.
Article in EBioMedicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
76 citing papers in PubMed, 108 citations in OpenAlex.
- Intact HIV-1 proviruses accumulate at distinct chromosomal positions during prolonged antiretroviral therapy.The Journal of clinical investigation · 2019Trial
- Hiding in Plain Sight: HIV-1 Membraneless Organelles as Nuclear Hubs-Host Hijacking, Replication, Immune Evasion, and Drug-Access Implications.Pathogens (Basel, Switzerland) · 2026Review
- Opportunities and challenges in achieving a functional cure for HIV.Infectious diseases & immunity · 2026Review
- The LEDGIN GS-9822 inhibits HIV-2 infection and enhances HIV-2 latency.Microbiology spectrum · 2026Article
- Is the molecular microenvironment of the latent HIV reservoir predictable using deep learning approaches?Journal of virology · 2026Review
- Block-and-Lock Approaches for HIV Cure: Mechanistic Insights, Challenges, and Emerging Role of CPSF6.International journal of molecular sciences · 2026Review
- Mechanistic insights and in vivo HIV suppression by the BRD4-targeting small molecule ZL0580.PLoS pathogens · 2026Article
- Review
- Oligomeric HIV-1 integrase structures reveal functional plasticity for intasome assembly and RNA binding.Nature communications · 2025Article
- Retrointegration2023-Papers from the 7th International Conference on Retroviral Integration.Viruses · 2025Article
- BRD4 modulator ZL0580 and LEDGINs additively block and lock HIV-1 transcription.Nature communications · 2025Article
- Disruption of LEDGF/p75-directed integration derepresses antisense transcription of the HIV-1 genome.bioRxiv : the preprint server for biology · 2024Article
- Review
- Long Terminal Repeats of Gammaretroviruses Retain Stable Expression after Integration Retargeting.Viruses · 2024Article
- Review
- The Impact of Lens Epithelium-Derived Growth Factor p75 Dimerization on Its Tethering Function.Cells · 2024Article
- The HIV-2 OGH double reporter virus shows that HIV-2 is less cytotoxic and less sensitive to reactivation from latency than HIV-1 in cell culture.Journal of virus eradication · 2023Article
- Biological and Structural Analyses of New Potent Allosteric Inhibitors of HIV-1 Integrase.Antimicrobial agents and chemotherapy · 2023Article
- HIV-1 capsid stability enables inositol phosphate-independent infection of target cells and promotes integration into genes.PLoS pathogens · 2023Article
- GS-9822, a preclinical LEDGIN candidate, displays a block-and-lock phenotype in cell culture.Antimicrobial agents and chemotherapy · 2023Article
16 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
Abstract
Persistence of latent, replication-competent Human Immunodeficiency Virus type 1 (HIV-1) provirus is the main impediment towards a cure for HIV/AIDS (Acquired Immune Deficiency Syndrome). Therefore, different therapeutic strategies to eliminate the viral reservoirs are currently being explored. We here propose a novel strategy to reduce the replicating HIV reservoir during primary HIV infection by means of drug-induced retargeting of HIV integration. A novel class of integration inhibitors, referred to as LEDGINs, inhibit the interaction between HIV integrase and the LEDGF/p75 host cofactor, the main determinant of lentiviral integration site selection. We show for the first time that LEDGF/p75 depletion hampers HIV-1 reactivation in cell culture. Next we demonstrate that LEDGINs relocate and retarget HIV integration resulting in a HIV reservoir that is refractory to reactivation by different latency-reversing agents. Taken together, these results support the potential of integrase inhibitors that modulate integration site targeting to reduce the likeliness of viral rebound.
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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.