ArticleRetrovirology2019
Impact of LEDGIN treatment during virus production on residual HIV-1 transcription.
Article in Retrovirology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- The LEDGIN GS-9822 inhibits HIV-2 infection and enhances HIV-2 latency.Microbiology spectrum · 2026Article
- Mechanistic insights and in vivo HIV suppression by the BRD4-targeting small molecule ZL0580.PLoS pathogens · 2026Article
- Harnessing antiviral RNAi therapeutics for pandemic viruses: SARS-CoV-2 and HIV.Drug delivery and translational research · 2025Review
- 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
- 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
- GS-9822, a preclinical LEDGIN candidate, displays a block-and-lock phenotype in cell culture.Antimicrobial agents and chemotherapy · 2023Article
- Review
- 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
- Article
- Allosteric Integrase Inhibitor Influences on HIV-1 Integration and Roles of LEDGF/p75 and HDGFL2 Host Factors.Viruses · 2022Article
- Targeted Nanocarrier Delivery of RNA Therapeutics to Control HIV Infection.Pharmaceutics · 2022Review
- Antiviral Activity and Resistance Profile of the Novel HIV-1 Non-Catalytic Site Integrase Inhibitor JTP-0157602.Journal of virology · 2022Article
- Complex of HIV-1 Integrase with Cellular Ku Protein: Interaction Interface and Search for Inhibitors.International journal of molecular sciences · 2022Article
- Article
- Review
- 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
- The chromatin landscape at the HIV-1 provirus integration site determines viral expression.Nucleic acids research · 2020Article
- Epigenetic crosstalk in chronic infection with HIV-1.Seminars in immunopathology · 2020Review
- Capsid-Labelled HIV To Investigate the Role of Capsid during Nuclear Import and Integration.Journal of virology · 2020Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundPersistence of latent, replication-competent provirus is the main impediment towards the cure of HIV infection. One of the critical questions concerning HIV latency is the role of integration site selection in HIV expression. Inhibition of the interaction between HIV integrase and its chromatin tethering cofactor LEDGF/p75 is known to reduce integration and to retarget residual provirus to regions resistant to reactivation. LEDGINs, small molecule inhibitors of the interaction between HIV integrase and LEDGF/p75, provide an interesting tool to study the underlying mechanisms. During early infection, LEDGINs block the interaction with LEDGF/p75 and allosterically inhibit the catalytic activity of IN (i.e. the early effect). When present during virus production, LEDGINs interfere with proper maturation due to enhanced IN oligomerization in the progeny virions (i.e. the late effect).
resultsWe studied the effect of LEDGINs present during virus production on the transcriptional state of the residual virus. Infection of cells with viruses produced in the presence of LEDGINs resulted in a residual reservoir that was refractory to activation. Integration of residual provirus was less favored near epigenetic markers associated with active transcription. However, integration near H3K36me3 and active genes, both targeted by LEDGF/p75, was not affected. Also in primary cells, LEDGIN treatment induced a reservoir resistant to activation due to a combined early and late effect.
conclusionLEDGINs present a research tool to study the link between integration and transcription, an essential question in retrovirology. LEDGIN treatment during virus production altered integration of residual provirus in a LEDGF/p75-independent manner, resulting in a reservoir that is refractory to activation.
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