ArticleProceedings of the National Academy of Sciences of the United States of America2013
Cleavage strongly influences whether soluble HIV-1 envelope glycoprotein trimers adopt a native-like conformation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 151 papers.
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Who cites it
151 citing papers in PubMed, 179 citations in OpenAlex.
- Rapid Boosting of HIV-1 Neutralizing Antibody Responses in Humans Following a Prolonged Immunologic Rest Period.The Journal of infectious diseases · 2019Trial
- Trial
- HIV-1 Env Heterogeneity: Cleavage, Trafficking, and Antigenic Consequences for Virions and Infected Cells.Viruses · 2026Review
- Non-human primate LIBRA-Seq accelerates neutralizing antibody discovery in RM vaccinated against HIV-1.PLoS pathogens · 2026Article
- Endocytic motif on HIV-1 Env regulates cleavage status and antibody neutralization of cell-free and cell-to-cell infection.Journal of virology · 2026Article
- Recent advances in HIV-1 envelope-based vaccine designs for guiding broadly neutralizing antibody response.Journal of virology · 2026Review
- Intranasal Delivery of HIV/SIV Antigens with NE/AS01B Adjuvants Enhances Cellular Immunity and Reduces Viral Loads in SHIV-Challenged Macaques.bioRxiv : the preprint server for biology · 2026Article
- The RV144 Trial Might Still Yield Useful Information.Current HIV research · 2026Review
- Ribonucleotide reductase subunit M2 mediates the mTOR pathway to recruit furin endoprotease and promote maturation of dengue virus.iScience · 2025Article
- Targeted bacteriophage T4 nanoparticles reverse HIV-1 latency in human T cell line models.iScience · 2025Article
- The HIV-1 envelope glycoprotein: structure, function and interactions with neutralizing antibodies.Nature reviews. Microbiology · 2025Review
- A modification to heptad repeat 1 of gp41 improves yield and/or quality of soluble pre-fusion HIV-1 envelope glycoprotein trimers.Journal of virology · 2025Article
- HIV-1 interaction with aniScience · 2024Article
- Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines.NPJ vaccines · 2024Article
- mRNA lipid nanoparticles expressing cell-surface cleavage independent HIV Env trimers elicit autologous tier-2 neutralizing antibodies.Frontiers in immunology · 2024Article
- Conformational antigenic heterogeneity as a cause of the persistent fraction in HIV-1 neutralization.Retrovirology · 2023Article
- Temsavir Modulates HIV-1 Envelope Conformation by Decreasing Its Proteolytic Cleavage.Viruses · 2023Article
- Conformational antigenic heterogeneity as a cause of the persistent fraction in HIV-1 neutralization.Research square · 2023Article
- Augmenting glycosylation-directed folding pathways enhances the fidelity of HIV Env immunogen production in plants.Biotechnology and bioengineering · 2022Article
- Broad and ultra-potent cross-clade neutralization of HIV-1 by a vaccine-induced CD4 binding site bovine antibody.Cell reports. Medicine · 2022Article
91 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
We compare the antigenicity and conformation of soluble, cleaved vs. uncleaved envelope glycoprotein (Env gp)140 trimers from the subtype A HIV type 1 (HIV-1) strain BG505. The impact of gp120-gp41 cleavage on trimer structure, in the presence or absence of trimer-stabilizing modifications (i.e., a gp120-gp41 disulfide bond and an I559P gp41 change, together designated SOSIP), was assessed. Without SOSIP changes, cleaved trimers disintegrate into their gp120 and gp41-ectodomain (gp41ECTO) components; when only the disulfide bond is present, they dissociate into gp140 monomers. Uncleaved gp140s remain trimeric whether SOSIP substitutions are present or not. However, negative-stain electron microscopy reveals that only cleaved trimers form homogeneous structures resembling native Env spikes on virus particles. In contrast, uncleaved trimers are highly heterogeneous, adopting a variety of irregular shapes, many of which appear to be gp120 subunits dangling from a central core that is presumably a trimeric form of gp41ECTO. Antigenicity studies with neutralizing and nonneutralizing antibodies are consistent with the EM images; cleaved, SOSIP-stabilized trimers express quaternary structure-dependent epitopes, whereas uncleaved trimers expose nonneutralizing gp120 and gp41ECTO epitopes that are occluded on cleaved trimers. These findings have adverse implications for using soluble, uncleaved trimers for structural studies, and the rationale for testing uncleaved trimers as vaccine candidates also needs to be reevaluated.
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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.