ArticleJournal of virology2007
Inhibition of human immunodeficiency virus type 1 concerted integration by strand transfer inhibitors which recognize a transient structural intermediate.
Article in Journal of virology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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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
28 citing papers in PubMed, 44 citations in OpenAlex.
- Delineation of a novel assembly intermediate in Rous sarcoma virus integration pathway.Nucleic acids research · 2026Article
- Retroviral integrase: Structure, mechanism, and inhibition.The Enzymes · 2021Article
- Inhibition of HTLV-1 Infection by HIV-1 First- and Second-Generation Integrase Strand Transfer Inhibitors.Frontiers in microbiology · 2019Article
- Retroviral integrase protein and intasome nucleoprotein complex structures.World journal of biological chemistry · 2017Review
- Rous sarcoma virus synaptic complex capable of concerted integration is kinetically trapped by human immunodeficiency virus integrase strand transfer inhibitors.The Journal of biological chemistry · 2014Article
- Inhibiting the HIV integration process: past, present, and the future.Journal of medicinal chemistry · 2014Article
- Critical appraisal of elvitegravir in the treatment of HIV-1/AIDS.HIV/AIDS (Auckland, N.Z.) · 2014Review
- A protein ballet around the viral genome orchestrated by HIV-1 reverse transcriptase leads to an architectural switch: from nucleocapsid-condensed RNA to Vpr-bridged DNA.Virus research · 2013Article
- Correlation of recombinant integrase activity and functional preintegration complex formation during acute infection by replication-defective integrase mutant human immunodeficiency virus.Journal of virology · 2012Article
- Raltegravir in HIV-1 infection: Safety and Efficacy in Treatment-naïve Patients.Clinical medicine reviews in therapeutics · 2011Article
- The HIV-1 integrase monomer induces a specific interaction with LTR DNA for concerted integration.Biochemistry · 2011Article
- HIV-1 integrase strand transfer inhibitors stabilize an integrase-single blunt-ended DNA complex.Journal of molecular biology · 2011Article
- A critical subset model provides a conceptual basis for the high antiviral activity of major HIV drugs.Science translational medicine · 2011Article
- Structural biology of retroviral DNA integration.Virology · 2011Review
- Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors.Biochemistry · 2010Article
- Structure-based modeling of the functional HIV-1 intasome and its inhibition.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Prospective strategies for targeting HIV-1 integrase function.Future medicinal chemistry · 2010Article
- Nucleoprotein intermediates in HIV-1 DNA integration visualized by atomic force microscopy.Journal of molecular biology · 2010Article
- Molecular Interactions between HIV-1 integrase and the two viral DNA ends within the synaptic complex that mediates concerted integration.Journal of molecular biology · 2009Article
- Identification of nevirapine-resistant HIV-1 in the latent reservoir after single-dose nevirapine to prevent mother-to-child transmission of HIV-1.The Journal of infectious diseases · 2009Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Human immunodeficiency virus type 1 (HIV-1) integrase (IN) inserts the viral DNA genome into host chromosomes. Here, by native agarose gel electrophoresis, using recombinant IN with a blunt-ended viral DNA substrate, we identified the synaptic complex (SC), a transient early intermediate in the integration pathway. The SC consists of two donor ends juxtaposed by IN noncovalently. The DNA ends within the SC were minimally processed (~15%). In a time-dependent manner, the SC associated with target DNA and progressed to the strand transfer complex (STC), the nucleoprotein product of concerted integration. In the STC, the two viral DNA ends are covalently attached to target and remain associated with IN. The diketo acid inhibitors and their analogs effectively inhibit HIV-1 replication by preventing integration in vivo. Strand transfer inhibitors L-870,810, L-870,812, and L-841,411, at low nM concentrations, effectively inhibited the concerted integration of viral DNA donor in vitro. The inhibitors, in a concentration-dependent manner, bound to IN within the SC and thereby blocked the docking onto target DNA, which thus prevented the formation of the STC. Although 3'-OH recessed donor efficiently formed the STC, reactions proceeding with this substrate exhibited marked resistance to the presence of inhibitor, requiring significantly higher concentrations for effective inhibition of all strand transfer products. These results suggest that binding of inhibitor to the SC occurs prior to, during, or immediately after 3'-OH processing. It follows that the IN-viral DNA complex is "trapped" by the strand transfer inhibitors via a transient intermediate within the cytoplasmic preintegration complex.
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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.