ArticleProceedings of the National Academy of Sciences of the United States of America2014
Stable, uncleaved HIV-1 envelope glycoprotein gp140 forms a tightly folded trimer with a native-like structure.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 67 citations in OpenAlex.
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- Functional Convergence of Genetically Diverse B-Cell Receptors in Simian-HIV Infected Rhesus Macaques.bioRxiv : the preprint server for biology · 2026Article
- HIV subtype-specific gp140-CD4 binding, Temsavir efficacy, and identification of novel adhesion inhibitors against Chinese HIV strains.Frontiers in immunology · 2025Article
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- Persistent immunogenicity of integrase defective lentiviral vectors delivering membrane-tethered native-like HIV-1 envelope trimers.NPJ vaccines · 2022Article
- Presentation of antigen on extracellular vesicles using transmembrane domains from viral glycoproteins for enhanced immunogenicity.Journal of extracellular vesicles · 2022Article
- Immunogenicity of stabilized HIV-1 Env trimers delivered by self-amplifying mRNA.Molecular therapy. Nucleic acids · 2021Article
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- HIV-infected macrophages resist efficient NK cell-mediated killing while preserving inflammatory cytokine responses.Cell host & microbe · 2021Article
- Photoimmunotherapy Using Cationic and Anionic Photosensitizer-Antibody Conjugates against HIV Env-Expressing Cells.International journal of molecular sciences · 2020Article
- Harnessing early life immunity to develop a pediatric HIV vaccine that can protect through adolescence.PLoS pathogens · 2020Article
- Probing the Structure of the HIV-1 Envelope Trimer Using Aspartate Scanning Mutagenesis.Journal of virology · 2020Article
- Cryo-EM Structure of Full-length HIV-1 Env Bound With the Fab of Antibody PG16.Journal of molecular biology · 2020Article
- Monoclonal Antibody 2C6 Targets a Cross-Clade Conformational Epitope in gp41 with Highly Active Antibody-Dependent Cell Cytotoxicity.Journal of virology · 2019Article
- AIDS Vaccine Research Subcommittee (AVRS) Consultation: Early-Life Immunization Strategies against HIV Acquisition.mSphere · 2019Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 4 countries.
Funding
Abstract
The HIV-1 envelope spike [trimeric (gp160)3, cleaved to (gp120/gp41)3] is the mediator of viral entry and the principal target of humoral immune response to the virus. Production of a recombinant preparation that represents the functional spike poses a challenge for vaccine development, because the (gp120/gp41)3 complex is prone to dissociation. We have reported previously that stable HIV-1 gp140 trimers, the uncleaved ectodomains of (gp160)3, have nearly all of the antigenic properties expected for native viral spikes. Because of recent claims that uncleaved gp140 proteins may adopt a nonnative structure with three gp120 moieties "dangling" from a trimeric gp41 ectodomain in its postfusion conformation, we have inserted a long, flexible linker between gp120 and gp41 in our stable gp140 trimers to assess their stability and to analyze their conformation in solution. The modified trimer has biochemical and antigenic properties virtually identical to those of its unmodified counterpart. Both forms bind a single CD4 per trimer, suggesting that the trimeric conformation occludes two of the three CD4 sites even when a flexible linker has relieved the covalent constraint between gp120 and gp41. In contrast, an artificial trimer containing three gp120s flexibly tethered to a trimerization tag binds three CD4s and has antigenicity nearly identical to that of monomeric gp120. Moreover, the gp41 part of both modified and unmodified gp140 trimers has a structure very different from that of postfusion gp41. These results show that uncleaved gp140 trimers from suitable isolates have compact, native-like structures and support their use as candidate vaccine immunogens.
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