ArticleJournal of acquired immune deficiency syndromes (1999)2011
Reduced replication capacity of NL4-3 recombinant viruses encoding reverse transcriptase-integrase sequences from HIV-1 elite controllers.
Article in Journal of acquired immune deficiency syndromes (1999), 2011. 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, 63 citations in OpenAlex.
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- Pol-Driven Replicative Capacity Impacts Disease Progression in HIV-1 Subtype C Infection.Journal of virology · 2018Article
- Understanding the CD8 T-cell response in natural HIV control.F1000Research · 2018Review
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- Identification of Interleukin-27 (IL-27)/IL-27 Receptor Subunit Alpha as a Critical Immune Axis forJournal of virology · 2017Article
- Impaired Downregulation of NKG2D Ligands by Nef Proteins from Elite Controllers Sensitizes HIV-1-Infected Cells to Antibody-Dependent Cellular Cytotoxicity.Journal of virology · 2017Article
- Accumulation of Pol Mutations Selected by HLA-B*52:01-C*12:02 Protective Haplotype-Restricted Cytotoxic T Lymphocytes Causes Low Plasma Viral Load Due to Low Viral Fitness of Mutant Viruses.Journal of virology · 2017Article
- Impaired human immunodeficiency virus type 1 replicative fitness in atypical viremic non-progressor individuals.AIDS research and therapy · 2017Article
- Novel Acylguanidine-Based Inhibitor of HIV-1.Journal of virology · 2016Article
- Population-Level Immune-Mediated Adaptation in HIV-1 Polymerase during the North American Epidemic.Journal of virology · 2016Observational
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- Nef Proteins from HIV-1 Elite Controllers Are Inefficient at Preventing Antibody-Dependent Cellular Cytotoxicity.Journal of virology · 2015Article
- Lack of a significant impact of Gag-Protease-mediated HIV-1 replication capacity on clinical parameters in treatment-naive Japanese individuals.Retrovirology · 2015Article
- Consequences of HLA-B*13-Associated Escape Mutations on HIV-1 Replication and Nef Function.Journal of virology · 2015Article
- Pairwise growth competition assay for determining the replication fitness of human immunodeficiency viruses.Journal of visualized experiments : JoVE · 2015Article
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundIdentifying viral and host determinants of HIV-1 elite control may help inform novel therapeutic and/or vaccination strategies. Previously, we observed decreased replication capacity in controller-derived viruses suggesting that fitness consequences of human leukocyte antigen (HLA) class I-associated escape mutations in Gag may contribute to this phenotype. This study examines whether similar functional defects occur in Pol proteins of elite controllers.
methodsRecombinant NL4-3 viruses encoding plasma RNA-derived reverse transcriptase-integrase sequences from 58 elite controllers and 50 untreated chronic progressors were constructed, and replication capacity measured in vitro using a green fluorescent protein (GFP) reporter T-cell assay. Sequences were analyzed for drug resistance and HLA-associated viral polymorphisms.
resultsController-derived viruses displayed significantly lower replication capacity compared with those from progressors (P < 0.0001). Among controllers, the most attenuated viruses were generated from individuals expressing HLA-B*57 or B*51. In viruses from B*57+ progressors (n = 8), a significant inverse correlation was observed between B*57-associated reverse transcriptase-integrase escape mutations and replication capacity (R = -0.89; P = 0.003); a similar trend was observed in B*57+ controller-derived viruses (n = 20, R = -0.36; P = 0.08).
conclusionsHIV-1 Pol function seemed to be compromised in elite controllers. As observed previously for Gag, HLA-associated immune pressure in Pol may contribute to viral attenuation and subsequent control of viremia.
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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.