ArticleJournal of virology2003
Variability at human immunodeficiency virus type 1 subtype C protease cleavage sites: an indication of viral fitness?
Article in Journal of virology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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.
The trial behind it
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
29 citing papers in PubMed, 73 citations in OpenAlex.
- Contribution of Gag and Protease to HIV-1 Phenotypic Drug Resistance in Pediatric Patients Failing Protease Inhibitor-Based Therapy.Antimicrobial agents and chemotherapy · 2016Trial
- HIV-1 diversity in an antiretroviral treatment naïve cohort from Bushbuckridge, Mpumalanga Province, South Africa.Virology journal · 2015Trial
- Chemogenetic ON and OFF switches for RNA virus replication.Nature communications · 2021Article
- Vaccine targeting SIVmac251 protease cleavage sites protects macaques against vaginal infection.The Journal of clinical investigation · 2020Article
- Modulation of HIV-1 Gag/Gag-Pol frameshifting by tRNA abundance.Nucleic acids research · 2019Article
- AnACS catalysis · 2019Article
- Overexpression, Purification and Functional Characterisation of Wild-Type HIV-1 Subtype C Protease and Two Variants Using a Thioredoxin and His-Tag Protein Fusion System.The protein journal · 2018Article
- A substrate selected by phage display exhibits enhanced side-chain hydrogen bonding to HIV-1 protease.Acta crystallographica. Section D, Structural biology · 2018Article
- Article
- Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaoundé, Cameroon.Scientific reports · 2017Article
- A novel HIV vaccine targeting the protease cleavage sites.AIDS research and therapy · 2017Review
- Evolutionary Analysis of HIV-1 Pol Proteins Reveals Representative Residues for Viral Subtype Differentiation.Frontiers in microbiology · 2017Article
- Toward the development of a single-round infection assay based on EGFP reporting for anti-HIV-1 drug discovery.Reports of biochemistry & molecular biology · 2015Article
- Genetic Changes in HIV-1 Gag-Protease Associated with Protease Inhibitor-Based Therapy Failure in Pediatric Patients.AIDS research and human retroviruses · 2015Article
- HIV-1 Gag C-terminal amino acid substitutions emerging under selective pressure of protease inhibitors in patient populations infected with different HIV-1 subtypes.Retrovirology · 2014Article
- New findings in cleavage sites variability across groups, subtypes and recombinants of human immunodeficiency virus type 1.PloS one · 2014Article
- The N-end rule and retroviral infection: no effect on integrase.Virology journal · 2013Article
- Effects of HIV-1 protease on cellular functions and their potential applications in antiretroviral therapy.Cell & bioscience · 2012Article
- Human Immunodeficiency Virus Gag and protease: partners in resistance.Retrovirology · 2012Review
- Structural, kinetic, and thermodynamic studies of specificity designed HIV-1 protease.Protein science : a publication of the Protein Society · 2012Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
Naturally occurring polymorphisms in the protease of human immunodeficiency virus type 1 (HIV-1) subtype C would be expected to lead to adaptive (compensatory) changes in protease cleavage sites. To test this hypothesis, we examined the prevalences and patterns of cleavage site polymorphisms in the Gag, Gag-Pol, and Nef cleavage sites of C compared to those in non-C subtypes. Codon-based maximum-likelihood methods were used to assess the natural selection and evolutionary history of individual cleavage sites. Seven cleavage sites (p17/p24, p24/p2, NC/p1, NC/TFP, PR/RT, RT/p66, and p66/IN) were well conserved over time and in all HIV-1 subtypes. One site (p1/p6(gag)) exhibited moderate variation, and four sites (p2/NC, TFP/p6(pol), p6(pol)/PR, and Nef) were highly variable, both within and between subtypes. Three of the variable sites are known to be major determinants of polyprotein processing and virion production. P2/NC controls the rate and order of cleavage, p6(gag) is an important phosphoprotein required for virion release, and TFP/p6(pol), a novel cleavage site in the transframe domain, influences the specificity of Gag-Pol processing and the activation of protease. Overall, 58.3% of the 12 HIV-1 cleavage sites were significantly more diverse in C than in B viruses. When analyzed as a single concatenated fragment of 360 bp, 96.0% of group M cleavage site sequences fell into subtype-specific phylogenetic clusters, suggesting that they coevolved with the virus. Natural variation at C cleavage sites may play an important role, not only in regulation of the viral cycle but also in disease progression and response to therapy.
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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.