ArticleJournal of virology2005
Anti-human immunodeficiency virus type 1 (HIV-1) antibodies 2F5 and 4E10 require surprisingly few crucial residues in the membrane-proximal external region of glycoprotein gp41 to neutralize HIV-1.
Article in Journal of virology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers.
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Who cites it
141 citing papers in PubMed, 275 citations in OpenAlex.
- Short Communication: A Recombinant Variant with Increased Envelope Entry Efficiency Emerged During Early Infection of an HIV-1 Subtype C Dual Infected Rapid Progressor.AIDS research and human retroviruses · 2016Trial
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- Evaluation of implementing drug checking services for anabolic androgenic steroids in Switzerland: a pilot study.Harm reduction journal · 2025Article
- Affinity gaps among B cells in germinal centers drive the selection of MPER precursors.Nature immunology · 2024Article
- Antigen-display exosomes provide adjuvant-free protection against SARS-CoV-2 disease at nanogram levels of spike protein.bioRxiv : the preprint server for biology · 2024Article
- MILKSHAKE Western blot and Sundae ELISA: We all scream for better antibody validation.Journal of immunological methods · 2023Article
- Displaying and delivering viral membrane antigens via WW domain-activated extracellular vesicles.Science advances · 2023Article
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- Dependence on a variable residue limits the breadth of an HIV MPER neutralizing antibody, despite convergent evolution with broadly neutralizing antibodies.PLoS pathogens · 2022Article
- Global Increases in Human Immunodeficiency Virus Neutralization Sensitivity Due to Alterations in the Membrane-Proximal External Region of the Envelope Glycoprotein Can Be Minimized by Distant State 1-Stabilizing Changes.Journal of virology · 2022Article
- Unique genotypic features of HIV-1 C gp41 membrane proximal external region variants during pregnancy relate to mother-to-child transmission via breastfeeding.Journal of clinical pediatrics and neonatology · 2021Article
- An MPER antibody neutralizes HIV-1 using germline features shared among donors.Nature communications · 2019Article
- Engineering of a Lectibody Targeting High-Mannose-Type Glycans of the HIV Envelope.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- Structural Basis for Epitopes in the gp120 Cluster A Region that Invokes Potent Effector Cell Activity.Viruses · 2019Review
- Identification of variant HIV envelope proteins with enhanced affinities for precursors to anti-gp41 broadly neutralizing antibodies.PloS one · 2019Article
- Reverse Immunology Approach to Define a New HIV-gp41-Neutralizing Epitope.Journal of immunology research · 2019Article
- Development of broadly neutralizing antibodies in HIV-1 infected elite neutralizers.Retrovirology · 2018Review
- The development of HIV vaccines targeting gp41 membrane-proximal external region (MPER): challenges and prospects.Protein & cell · 2018Review
- Article
81 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
The conserved membrane-proximal external region (MPER) of human immunodeficiency virus type 1 (HIV-1) gp41 is a target of two broadly neutralizing human monoclonal antibodies, 2F5 and 4E10, and is an important lead for vaccine design. However, immunogens that bear MPER epitopes so far have not elicited neutralizing antibodies in laboratory animals. One explanation is that the immunogens fail to recreate the proper molecular environment in which the epitopes of 2F5 and 4E10 are presented on the virus. To explore this molecular environment, we used alanine-scanning mutagenesis across residues 660 to 680 in the MPER of a pseudotyped variant of HIV-1(JR-FL), designated HIV-1(JR2), and examined the ability of 2F5 and 4E10 to neutralize the Ala mutant viruses. The results show that the only changes to produce neutralization resistance to 2F5 occurred in residue D, K, or W of the core epitope (LELDKWANL). Likewise, 4E10 resistance arose by replacing one of three residues; two (W and F) were in the core epitope, and one (W) was seven residues C-terminal to these two (NWFDISNWLW). Importantly, no single substitution resulted in resistance of virus to both 2F5 and 4E10. Surprisingly, 8 out of 21 MPER Ala mutants were more sensitive than the parental pseudovirus to 2F5 and/or 4E10. At most, only small differences in neutralization sensitivity to anti-gp120 monoclonal antibody b12 and peptide T20 were observed with the MPER Ala mutant pseudoviruses. These data suggest that MPER substitutions can act locally and enhance the neutralizing activity of antibodies to this region and imply a distinct role of the MPER of gp41 during HIV-1 envelope-mediated fusion. Neutralization experiments showing synergy between and T20 and 4E10 against HIV-1 are also presented. The data presented may aid in the design of antigens that better present the MPER of gp41 to the immune system.
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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.