ArticlePLoS biology2019
CD4 occupancy triggers sequential pre-fusion conformational states of the HIV-1 envelope trimer with relevance for broadly neutralizing antibody activity.
Article in PLoS biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- Article
- Conformational activation and disulfide exchange in HIV-1 Env induce cell-free lytic/fusogenic transformation and enhance infection.Journal of virology · 2025Article
- Viral glycoprotein-mediated entry and antibody-mediated immunity in HIV-1 and SARS-CoV-2 infection.Frontiers in immunology · 2025Review
- Assessing bnAb potency in the context of HIV-1 envelope conformational plasticity.PLoS pathogens · 2025Article
- Conformational flexibility of HIV-1 envelope glycoproteins modulates transmitted/founder sensitivity to broadly neutralizing antibodies.Nature communications · 2024Article
- Inhibition of human immunodeficiency virus (HIV-1) infectivity by expression of poorly or broadly neutralizing antibodies against Env in virus-producing cells.Journal of virology · 2024Article
- Conformational flexibility of HIV-1 envelope glycoproteins modulates transmitted / founder sensitivity to broadly neutralizing antibodies.bioRxiv : the preprint server for biology · 2023Article
- Broadly neutralizing antibody epitopes on HIV-1 particles are exposed after virus interaction with host cells.Journal of virology · 2023Article
- Trapping the HIV-1 V3 loop in a helical conformation enables broad neutralization.Nature structural & molecular biology · 2023Article
- Article
- Regulation of epitope exposure in the gp41 membrane-proximal external region through interactions at the apex of HIV-1 Env.PLoS pathogens · 2022Article
- Asymmetric Structures and Conformational Plasticity of the Uncleaved Full-Length Human Immunodeficiency Virus Envelope Glycoprotein Trimer.Journal of virology · 2021Article
- Distinct conformations of the HIV-1 V3 loop crown are targetable for broad neutralization.Nature communications · 2021Article
- Altered Env conformational dynamics as a mechanism of resistance to peptide-triazole HIV-1 inactivators.Retrovirology · 2021Article
- Peptide Triazole Thiol Irreversibly Inactivates Metastable HIV-1 Env by Accessing Conformational Triggers Intrinsic to Virus-Cell Entry.Microorganisms · 2021Article
- Dual Pathways of Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Trafficking Modulate the Selective Exclusion of Uncleaved Oligomers from Virions.Journal of virology · 2021Article
- To bnAb or Not to bnAb: Defining Broadly Neutralising Antibodies Against HIV-1.Frontiers in immunology · 2021Review
- A bipartite structural organization defines the SERINC family of HIV-1 restriction factors.Nature structural & molecular biology · 2020Article
- Molecular Mechanism of HIV-1 Entry.Trends in microbiology · 2019Review
- Broadly resistant HIV-1 against CD4-binding site neutralizing antibodies.PLoS pathogens · 2019Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During the entry process, the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer undergoes a sequence of conformational changes triggered by both CD4 and coreceptor engagement. Resolving the conformation of these transient entry intermediates has proven challenging. Here, we fine-mapped the antigenicity of entry intermediates induced by increasing CD4 engagement of cell surface-expressed Env. Escalating CD4 triggering led to the sequential adoption of different pre-fusion conformational states of the Env trimer, up to the pre-hairpin conformation, that we assessed for antibody epitope presentation. Maximal accessibility of the coreceptor binding site was detected below Env saturation by CD4. Exposure of the fusion peptide and heptad repeat 1 (HR1) required higher CD4 occupancy. Analyzing the diverse antigenic states of the Env trimer, we obtained key insights into the transitions in epitope accessibility of broadly neutralizing antibodies (bnAbs). Several bnAbs preferentially bound CD4-triggered Env, indicating a potential capacity to neutralize both pre- and post-CD4 engagement, which needs to be explored. Assessing binding and neutralization activity of bnAbs, we confirm antibody dissociation rates as a driver of incomplete neutralization. Collectively, our findings highlight a need to resolve Env conformations that are neutralization-relevant to provide guidance for immunogen development.
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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.