ArticlePLoS pathogens2016
Saturation Mutagenesis of the HIV-1 Envelope CD4 Binding Loop Reveals Residues Controlling Distinct Trimer Conformations.
Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed, 27 citations in OpenAlex.
- Scanning the horizon: deep mutational scanning approaches in virology.Journal of virology · 2026Review
- Mapping the mutational landscape of an avian retrovirus envelope protein across its evolutionary trajectory.PLoS pathogens · 2026Article
- Epitope mapping via in vitro deep mutational scanning methods and its applications.The Journal of biological chemistry · 2025Review
- Implications of the 375W mutation for HIV-1 tropism and vaccine development.Journal of virology · 2024Article
- ProteinGym: Large-Scale Benchmarks for Protein Design and Fitness Prediction.bioRxiv : the preprint server for biology · 2023Article
- Article
- Genotype-phenotype landscapes for immune-pathogen coevolution.Trends in immunology · 2023Review
- Mutational fitness landscape and drug resistance.Current opinion in structural biology · 2023Review
- Cross-Neutralizing CRF01_AE-Infected Plasma from Malaysia Targets CD4-Binding Site of Human Immunodeficiency Virus Type-1 Envelope Glycoprotein.AIDS research and human retroviruses · 2022Article
- Engineering well-expressed, V2-immunofocusing HIV-1 envelope glycoprotein membrane trimers for use in heterologous prime-boost vaccine regimens.PLoS pathogens · 2021Article
- Deep Mutational Scanning of Viral Glycoproteins and Their Host Receptors.Frontiers in molecular biosciences · 2021Review
- Stoichiometric Analyses of Soluble CD4 to Native-like HIV-1 Envelope by Single-Molecule Fluorescence Spectroscopy.Cell reports · 2019Article
- Constrained Mutational Sampling of Amino Acids in HIV-1 Protease Evolution.Molecular biology and evolution · 2019Article
- Article
- Envelope glycoproteins sampling states 2/3 are susceptible to ADCC by sera from HIV-1-infected individuals.Virology · 2018Article
- HIV-1 R5 Macrophage-Tropic Envelope Glycoprotein Trimers Bind CD4 with High Affinity, while the CD4 Binding Site on Non-macrophage-tropic, T-Tropic R5 Envelopes Is Occluded.Journal of virology · 2018Article
- An entry-competent intermediate state of the HIV-1 envelope glycoproteins.Receptors & clinical investigation · 2017Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The conformation of HIV-1 envelope (Env) glycoprotein trimers is key in ensuring protection against waves of neutralizing antibodies generated during infection, while maintaining sufficient exposure of the CD4 binding site (CD4bs) for viral entry. The CD4 binding loop on Env is an early contact site for CD4 while penetration of a proximal cavity by CD4 triggers Env conformational changes for entry. The role of residues in the CD4 binding loop in regulating the conformation of the trimer and trimer association domain (TAD) was investigated using a novel saturation mutagenesis approach. Single mutations identified, resulted in distinct trimer conformations affecting CD4bs exposure, the glycan shield and the TAD across diverse HIV-1 clades. Importantly, mutations that improve access to the CD4bs without exposing the immunodominant V3 loop were identified. The different trimer conformations identified will affect the specificity and breadth of nabs elicited in vivo and are important to consider in design of Env immunogens for vaccines.
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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.