ArticleJournal of virology2005
Mutations that abrogate human immunodeficiency virus type 1 reverse transcriptase dimerization affect maturation of the reverse transcriptase heterodimer.
Article in Journal of virology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 60 citations in OpenAlex.
- Mechanisms of HIV-1 assembly, release and maturation.Nature reviews. Microbiology · 2026Review
- Lactic acid produced by optimal vaginal Lactobacillus spp. potently and specifically inactivates HIV-1 in vitro by targeting the viral RNA genome and reverse transcriptase.PLoS pathogens · 2025Article
- Cryo-EM structure of human telomerase dimer reveals H/ACA RNP-mediated dimerization.Science (New York, N.Y.) · 2025Article
- HIV-1 reverse transcriptase stability correlates with Gag cleavage efficiency: reverse transcriptase interaction implications for modulating protease activation.Journal of virology · 2023Article
- Cryo-EM structure of the HIV-1 Pol polyprotein provides insights into virion maturation.Science advances · 2022Article
- Relative domain orientation of the L289K HIV-1 reverse transcriptase monomer.Protein science : a publication of the Protein Society · 2022Article
- HIV-1 gp120 Antagonists Also Inhibit HIV-1 Reverse Transcriptase by Bridging the NNRTI and NRTI Sites.Journal of medicinal chemistry · 2021Article
- Retroviral RNase H: Structure, mechanism, and inhibition.The Enzymes · 2021Review
- Article
- Binding interface and impact on protease cleavage for an RNA aptamer to HIV-1 reverse transcriptase.Nucleic acids research · 2020Article
- Conformational Changes in HIV-1 Reverse Transcriptase that Facilitate Its Maturation.Structure (London, England : 1993) · 2019Article
- HIV-1-based Virus-like Particles that Morphologically Resemble Mature, Infectious HIV-1 Virions.Viruses · 2019Article
- Molecular dissection of an inhibitor targeting the HIV integrase dependent preintegration complex nuclear import.Cellular microbiology · 2019Article
- Article
- Differential Evolution of Antiretroviral Restriction Factors in Pteropid Bats as Revealed by APOBEC3 Gene Complexity.Molecular biology and evolution · 2018Article
- Effect of tRNA on the Maturation of HIV-1 Reverse Transcriptase.Journal of molecular biology · 2018Article
- Molecular Docking Studies of HIV-1 Resistance to Reverse Transcriptase Inhibitors: Mini-Review.Molecules (Basel, Switzerland) · 2018Review
- NMR structure of the HIV-1 reverse transcriptase thumb subdomain.Journal of biomolecular NMR · 2016Article
- An Essential Role of INI1/hSNF5 Chromatin Remodeling Protein in HIV-1 Posttranscriptional Events and Gag/Gag-Pol Stability.Journal of virology · 2016Article
- Structural Maturation of HIV-1 Reverse Transcriptase-A Metamorphic Solution to Genomic Instability.Viruses · 2016Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The specific impact of mutations that abrogate human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) dimerization on virus replication is not known, as mutations shown previously to inhibit RT dimerization also impact Gag-Pol stability, resulting in pleiotropic effects on HIV-1 replication. We have previously characterized mutations at codon 401 in the HIV-1 RT tryptophan repeat motif that abrogate RT dimerization in vitro, leading to a loss in polymerase activity. The introduction of the RT dimerization-inhibiting mutations W401L and W401A into HIV-1 resulted in the formation of noninfectious viruses with reduced levels of both virion-associated and intracellular RT activity compared to the wild-type virus and the W401F mutant, which does not inhibit RT dimerization in vitro. Steady-state levels of the p66 and p51 RT subunits in viral lysates of the W401L and W401A mutants were reduced, but no significant decrease in Gag-Pol was observed compared to the wild type. In contrast, there was a decrease in processing of p66 to p51 in cell lysates for the dimerization-defective mutants compared to the wild type. The treatment of transfected cells with indinavir suggested that the HIV-1 protease contributed to the degradation of virion-associated RT subunits. These data demonstrate that mutations near the RT dimer interface that abrogate RT dimerization in vitro result in the production of replication-impaired viruses without detectable effects on Gag-Pol stability or virion incorporation. The inhibition of RT activity is most likely due to a defect in RT maturation, suggesting that RT dimerization represents a valid drug target for chemotherapeutic intervention.
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