ArticleJournal of virology2010
The effect of clade-specific sequence polymorphisms on HIV-1 protease activity and inhibitor resistance pathways.
Article in Journal of virology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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.
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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
20 citing papers in PubMed, 38 citations in OpenAlex.
- Design, Synthesis, and Biological Evaluation of Darunavir Analogs as HIV-1 Protease Inhibitors.ACS bio & med chem Au · 2024Article
- Non-coding RNAs and retroviruses.Retrovirology · 2018Review
- Decoding HIV resistance: from genotype to therapy.Future medicinal chemistry · 2017Review
- MicroRNAs as Important Players in Host-Adenovirus Interactions.Frontiers in microbiology · 2017Review
- Effects of Hinge-region Natural Polymorphisms on Human Immunodeficiency Virus-Type 1 Protease Structure, Dynamics, and Drug Pressure Evolution.The Journal of biological chemistry · 2016Article
- Pulsed EPR characterization of HIV-1 protease conformational sampling and inhibitor-induced population shifts.Physical chemistry chemical physics : PCCP · 2016Article
- Production of Mucosally Transmissible SHIV Challenge Stocks from HIV-1 Circulating Recombinant Form 01_AE env Sequences.PLoS pathogens · 2016Article
- Non-coding RNAs and HIV: viral manipulation of host dark matter to shape the cellular environment.Frontiers in genetics · 2015Review
- HIV-1 protease-substrate coevolution in nelfinavir resistance.Journal of virology · 2014Article
- The role of select subtype polymorphisms on HIV-1 protease conformational sampling and dynamics.The Journal of biological chemistry · 2014Article
- Article
- Evolutionary biochemistry: revealing the historical and physical causes of protein properties.Nature reviews. Genetics · 2013Review
- Elucidating a relationship between conformational sampling and drug resistance in HIV-1 protease.Biochemistry · 2013Article
- Inhibitor-induced conformational shifts and ligand-exchange dynamics for HIV-1 protease measured by pulsed EPR and NMR spectroscopy.The journal of physical chemistry. B · 2012Article
- Correlating conformational shift induction with altered inhibitor potency in a multidrug resistant HIV-1 protease variant.Biochemistry · 2012Article
- HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements.Biochemistry · 2012Article
- In Silico and In Vitro Comparison of HIV-1 Subtypes B and CRF02_AG Integrases Susceptibility to Integrase Strand Transfer Inhibitors.Advances in virology · 2012Article
- Accessory mutations maintain stability in drug-resistant HIV-1 protease.Journal of molecular biology · 2011Article
- Clinical management of HIV drug resistance.Viruses · 2011Review
- Molecular Basis for Drug Resistance in HIV-1 Protease.Viruses · 2010Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
The majority of HIV-1 infections around the world result from non-B clade HIV-1 strains. The CRF01_AE (AE) strain is seen principally in Southeast Asia. AE protease differs by approximately 10% in amino acid sequence from clade B protease and carries several naturally occurring polymorphisms that are associated with drug resistance in clade B. AE protease has been observed to develop resistance through a nonactive-site N88S mutation in response to nelfinavir (NFV) therapy, whereas clade B protease develops both the active-site mutation D30N and the nonactive-site mutation N88D. Structural and biochemical studies were carried out with wild-type and NFV-resistant clade B and AE protease variants. The relationship between clade-specific sequence variations and pathways to inhibitor resistance was also assessed. AE protease has a lower catalytic turnover rate than clade B protease, and it also has weaker affinity for both NFV and darunavir (DRV). This weaker affinity may lead to the nonactive-site N88S variant in AE, which exhibits significantly decreased affinity for both NFV and DRV. The D30N/N88D mutations in clade B resulted in a significant loss of affinity for NFV and, to a lesser extent, for DRV. A comparison of crystal structures of AE protease shows significant structural rearrangement in the flap hinge region compared with those of clade B protease and suggests insights into the alternative pathways to NFV resistance. In combination, our studies show that sequence polymorphisms within clades can alter protease activity and inhibitor binding and are capable of altering the pathway to inhibitor resistance.
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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.