ReviewCurrent topics in microbiology and immunology2015
HIV-1 integrase multimerization as a therapeutic target.
Review in Current topics in microbiology and immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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.
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Who cites it
19 citing papers in PubMed, 47 citations in OpenAlex.
- Isolation of New Chemical Modulators of the Interaction Between HIV-1 Integrase and the Cellular Restriction Factor GCN2.Viruses · 2025Article
- TAR RNA Mimicry of INI1 and Its Influence on Non-Integration Function of HIV-1 Integrase.Viruses · 2025Review
- Article
- The structural and mechanistic bases for the viral resistance to allosteric HIV-1 integrase inhibitor pirmitegravir.bioRxiv : the preprint server for biology · 2024Article
- In search of therapeutic candidates for HIV/AIDS: rational approaches, design strategies, structure-activity relationship and mechanistic insights.RSC advances · 2021Review
- Retroviral integrase: Structure, mechanism, and inhibition.The Enzymes · 2021Article
- Exploring the Free-Energy Landscape and Thermodynamics of Protein-Protein Association.Biophysical journal · 2020Article
- Going beyond Integration: The Emerging Role of HIV-1 Integrase in Virion Morphogenesis.Viruses · 2020Review
- HIV-1 Maturation: Lessons Learned from Inhibitors.Viruses · 2020Review
- The role of integration and clonal expansion in HIV infection: live long and prosper.Retrovirology · 2018Review
- Synthesis and Evaluation of Aryl Quinolines as HIV-1 Integrase Multimerization Inhibitors.ACS medicinal chemistry letters · 2018Article
- Critical Contribution of Tyr15 in the HIV-1 Integrase (IN) in Facilitating IN Assembly and Nonenzymatic Function through the IN Precursor Form with Reverse Transcriptase.Journal of virology · 2017Article
- Computational and synthetic approaches for developing Lavendustin B derivatives as allosteric inhibitors of HIV-1 integrase.European journal of medicinal chemistry · 2016Article
- A New Class of Allosteric HIV-1 Integrase Inhibitors Identified by Crystallographic Fragment Screening of the Catalytic Core Domain.The Journal of biological chemistry · 2016Article
- Allosteric HIV-1 integrase inhibitors promote aberrant protein multimerization by directly mediating inter-subunit interactions: Structural and thermodynamic modeling studies.Protein science : a publication of the Protein Society · 2016Article
- The Preserved HTH-Docking Cleft of HIV-1 Integrase Is Functionally Critical.Structure (London, England : 1993) · 2016Article
- The Competitive Interplay between Allosteric HIV-1 Integrase Inhibitor BI/D and LEDGF/p75 during the Early Stage of HIV-1 Replication Adversely Affects Inhibitor Potency.ACS chemical biology · 2016Article
- A novel assay for screening inhibitors targeting HIV-1 integrase dimerization based on Ni-NTA magnetic agarose beads.Scientific reports · 2016Article
- Multifunctional facets of retrovirus integrase.World journal of biological chemistry · 2015Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Multimeric HIV-1 integrase (IN) plays an essential, multifunctional role in virus replication and serves as an important therapeutic target. Structural and biochemical studies have revealed the importance of the ordered interplay between IN molecules for its function. In the presence of viral DNA ends, individual IN subunits assemble into a tetramer and form a stable synaptic complex (SSC), which mediates integration of the reverse transcribed HIV-1 genome into chromatin. Cellular chromatin-associated protein LEDGF/p75 engages the IN tetramer in the SSC and directs HIV-1 integration into active genes. A mechanism to deregulate the productive interplay between IN subunits with small molecule inhibitors has recently received considerable attention. Most notably, allosteric IN inhibitors (ALLINIs) have been shown to bind to the IN dimer interface at the LEDGF/p75 binding pocket, stabilize interacting IN subunits, and promote aberrant, higher order IN multimerization. Consequently, these compounds impair formation of the SSC and associated LEDGF/p75-independent IN catalytic activities as well as inhibit LEDGF/p75 binding to the SSC in vitro. However, in infected cells, ALLINIs more potently impaired correct maturation of virus particles than the integration step. ALLINI treatments induced aberrant, higher order IN multimerization in virions and resulted in eccentric, non-infectious virus particles. These studies have suggested that the correctly ordered IN structure is important for virus particle morphogenesis and highlighted IN multimerization as a plausible therapeutic target for developing new inhibitors to enhance treatment options for HIV-1-infected patients.
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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.