ArticleJournal of virology2009
A quantitative affinity-profiling system that reveals distinct CD4/CCR5 usage patterns among human immunodeficiency virus type 1 and simian immunodeficiency virus strains.
Article in Journal of virology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
What it found
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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
79 citing papers in PubMed, 95 citations in OpenAlex.
- Compartmentalized replication of R5 T cell-tropic HIV-1 in the central nervous system early in the course of infection.PLoS pathogens · 2015Trial
- HIV-1 clinical isolates resistant to CCR5 antagonists exhibit delayed entry kinetics that are corrected in the presence of drug.Journal of virology · 2012Trial
- HIV-1 compartmentalization in the central nervous system during cryptococcal meningitis: Analysis of viral, fungal, and host factors.PLoS pathogens · 2026Article
- Kozak sequence libraries for systematically characterizing transgenes across expression levels.Nucleic acids research · 2026Article
- A New Type of Nonsuppressible Viremia Produced by HIV-Infected Macrophage.The Journal of infectious diseases · 2026Article
- Coreceptor usage of plasma and cerebrospinal fluid-derived HIV-1 subtype C variants.Virology journal · 2026Article
- Divergent HIV-1 Restriction Phenotypes of IFITMs Expressed in Target Cells and Incorporated into Virions.Biomolecules · 2026Article
- Neurosymptomatic Cerebrospinal Fluid Escape Is a Central Nervous System-Focused Form of Antiretroviral Therapy Treatment Failure.Open forum infectious diseases · 2026Article
- A New Type of Nonsuppressible Viremia Produced by HIV-Infected Macrophage.bioRxiv : the preprint server for biology · 2025Article
- Article
- Neurosymptomatic HIV-1 CSF escape is associated with replication in CNS T cells and inflammation.The Journal of clinical investigation · 2024Article
- Article
- Brain microglia serve as a persistent HIV reservoir despite durable antiretroviral therapy.The Journal of clinical investigation · 2023Article
- Protein overexpression can induce the elongation of cell membrane nanodomains.Biophysical journal · 2023Article
- Allogeneic gene-edited HIV-specific CAR-T cells secreting PD-1 blocking scFv enhance specific cytotoxic activity against HIV EnvVirologica Sinica · 2023Article
- Biotypes of Central Nervous System Complications in People With Human Immunodeficiency Virus: Virology, Immunology, and Neuropathology.The Journal of infectious diseases · 2023Article
- Evolution Driven By A Varying Host Environment Selects For Distinct HIV-1 Entry Phenotypes and Other Informative Variants.Frontiers in virology (Lausanne, Switzerland) · 2023Article
- Characterization of Macrophage-Tropic HIV-1 Infection of Central Nervous System Cells and the Influence of Inflammation.Journal of virology · 2022Article
- Variations in Cell Surface ACE2 Levels Alter Direct Binding of SARS-CoV-2 Spike Protein and Viral Infectivity: Implications for Measuring Spike Protein Interactions with Animal ACE2 Orthologs.Journal of virology · 2022Article
- Enhancement of CD4 Binding, Host Cell Entry, and Sensitivity to CD4bs Antibody Inhibition Conferred by a Natural but Rare Polymorphism in the HIV-1 Envelope.Journal of virology · 2022Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
The affinity of human immunodeficiency virus (HIV) envelope for CD4 and CCR5 appears to be associated with aspects of R5 virus (virus using the CCR5 coreceptor) pathogenicity. However, entry efficiency results from complex interactions between the viral envelope glycoprotein and both CD4 and CCR5, which limits attempts to correlate viral pathogenicity with surrogate measures of envelope CD4 and CCR5 affinities. Here, we present a system that provides a quantitative and comprehensive characterization of viral entry efficiency as a direct interdependent function of both CD4 and CCR5 levels. This receptor affinity profiling system also revealed heretofore unappreciated complexities underlying CD4/CCR5 usage. We first developed a dually inducible cell line in which CD4 and CCR5 could be simultaneously and independently regulated within a physiologic range of surface expression. Infection by multiple HIV type 1 (HIV-1) and simian immunodeficiency virus isolates could be examined simultaneously for up to 48 different combinations of CD4/CCR5 expression levels, resulting in a distinct usage pattern for each virus. Thus, each virus generated a unique three-dimensional surface plot in which viral infectivity varied as a function of both CD4 and CCR5 expression. From this functional form, we obtained a sensitivity vector along with corresponding metrics that quantified an isolate's overall efficiency of CD4/CCR5 usage. When applied to viral isolates with well-characterized sensitivities to entry/fusion inhibitors, the vector metrics were able to encapsulate their known biological phenotypes. The application of the vector metrics also indicated that envelopes derived from elite suppressors had overall-reduced entry efficiencies compared to those of envelopes derived from chronically infected viremic progressors. Our affinity-profiling system may help to refine studies of R5 virus tropism and pathogenesis.
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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.