ArticleProceedings of the National Academy of Sciences of the United States of America2012
Kinetic mechanism for HIV-1 neutralization by antibody 2G12 entails reversible glycan binding that slows cell entry.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 37 citations in OpenAlex.
- HIV-1 BG505 SOSIP immunization induced B cell expansion targeting the 465-glycan hole, with neutralizing antibodies exhibiting distinct binding modes and mechanisms of virus inhibition.PLoS pathogens · 2026Article
- Antiviral neutralizing antibodies: from in vitro to in vivo activity.Nature reviews. Immunology · 2023Review
- Article
- To bnAb or Not to bnAb: Defining Broadly Neutralising Antibodies Against HIV-1.Frontiers in immunology · 2021Review
- Closing and Opening Holes in the Glycan Shield of HIV-1 Envelope Glycoprotein SOSIP Trimers Can Redirect the Neutralizing Antibody Response to the Newly Unmasked Epitopes.Journal of virology · 2019Article
- Antibody responses to the HIV-1 envelope high mannose patch.Advances in immunology · 2019Review
- CD4 occupancy triggers sequential pre-fusion conformational states of the HIV-1 envelope trimer with relevance for broadly neutralizing antibody activity.PLoS biology · 2019Article
- HIV-1 inhibitory properties of eCD4-Igmim2 determined using an Env-mediated membrane fusion assay.PloS one · 2018Article
- Broadly Neutralizing Antibodies Display Potential for Prevention of HIV-1 Infection of Mucosal Tissue Superior to That of Nonneutralizing Antibodies.Journal of virology · 2017Article
- Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design.Annual review of immunology · 2016Review
- Capacity of Broadly Neutralizing Antibodies to Inhibit HIV-1 Cell-Cell Transmission Is Strain- and Epitope-Dependent.PLoS pathogens · 2015Article
- Antigenic properties of the human immunodeficiency virus envelope glycoprotein gp120 on virions bound to target cells.PLoS pathogens · 2015Article
- Engineering and exploitation of a fluorescent HIV-1 gp120 for live cell CD4 binding assays.Virology · 2015Article
- HIV: Potency needs constancy.Nature · 2014Article
- Structure of 2G12 Fab2 in complex with soluble and fully glycosylated HIV-1 Env by negative-stain single-particle electron microscopy.Journal of virology · 2014Article
- Functions of Antibodies.Microbiology spectrum · 2014Article
- Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits.Retrovirology · 2014Article
- Reversible and efficient activation of HIV-1 cell entry by a tyrosine-sulfated peptide dissects endocytic entry and inhibitor mechanisms.Journal of virology · 2014Article
- Glycotherapy: new advances inspire a reemergence of glycans in medicine.Chemistry & biology · 2014Review
- Differential glycosylation of envelope gp120 is associated with differential recognition of HIV-1 by virus-specific antibodies and cell infection.AIDS research and therapy · 2014Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Despite structural knowledge of broadly neutralizing monoclonal antibodies (NMAbs) complexed to HIV-1 gp120 and gp41 envelope glycoproteins, virus inactivation mechanisms have been difficult to prove, in part because neutralization assays are complex and were previously not understood. Concordant with recent evidence that HIV-1 titers are determined by a race between entry of cell-attached virions and competing inactivation processes, we show that NMAb 2G12, which binds to gp120 N-glycans with α (1, 2)-linked mannose termini and inhibits replication after passive transfer into patients, neutralizes by slowing entry of adsorbed virions. Accordingly, apparent neutralization is attenuated when a kinetically competing virus inactivation pathway is blocked. Moreover, removing 2G12 from media causes its dissociation from virions coupled to accelerated entry and restored infectivity, demonstrating the reversibility of neutralization. A difference between 2G12 dissociation and infectivity recovery rates implies that the inhibited complexes at virus-cell junctions contain several 2G12's that must dissociate before entry commences. Quantitative microscopy of 2G12 binding and dissociation from single virions and studies using a split CCR5 coreceptor suggest that 2G12 competitively inhibits interactions between gp120's V3 loop and the tyrosine sulfate-containing CCR5 amino terminus, thereby reducing assembly of complexes that catalyze entry. These results reveal a unique reversible kinetic mechanism for neutralization by an antibody that binds near a critical V3 region in the glycan shield of gp120.
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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.