title: Recognition of membrane-bound fusion-peptide/MPER complexes by the HIV-1 neutralizing 2F5 antibody: implications for anti-2F5 immunogenicity.
abstract: The membrane proximal external region (MPER) of the fusogenic HIV-1 glycoprotein-41 harbors the epitope sequence recognized by 2F5, a broadly neutralizing antibody isolated from an infected individual. Structural mimicry of the conserved MPER 2F5 epitope constitutes a pursued goal in the field of anti-HIV vaccine development. It has been proposed that 2F5 epitope folding into its native state is attained in the vicinity of the membrane interface and might involve interactions with other viral structures. Here we present results indicating that oligomeric complexes established between MPER and the conserved amino-terminal fusion peptide (FP) can partition into lipid vesicles and be specifically bound by the 2F5 antibody at their surfaces. Cryo-transmission electron microscopy of liposomes doped with MPER:FP peptide mixtures provided the structural grounds for complex recognition by antibody at lipid bilayer surfaces. Supporting the immunogenicity of the membrane-bound complex, these MPER:FP peptide-vesicle formulations could trigger cross-reactive anti-MPER antibodies in rabbits. Thus, our observations suggest that contacts with N-terminal regions of gp41 may stabilize the 2F5 epitope as a membrane-surface antigen.
authors.affiliation: Biophysics Unit (CSIC-UPV/EHU) and Biochemistry and Molecular Biology Department, University of the Basque Country (UPV/EHU), Bilbao, Spain.
authors.forename: Nerea
authors.initials: N
authors.lastname: Huarte
authors.forename: Aitziber
authors.initials: A
authors.lastname: Araujo
authors.forename: Rocio
authors.initials: R
authors.lastname: Arranz
authors.forename: Maier
authors.initials: M
authors.lastname: Lorizate
authors.forename: Heribert
authors.initials: H
authors.lastname: Quendler
authors.forename: Renate
authors.initials: R
authors.lastname: Kunert
authors.forename: José M
authors.initials: JM
authors.lastname: Valpuesta
authors.forename: José L
authors.initials: JL
authors.lastname: Nieva
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D057134:Antibodies, Neutralizing / Q000276:immunology* / Q000378:metabolism; D000939:Epitopes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D015483:HIV Antibodies / Q000276:immunology* / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry / Q000276:immunology; D046911:Macromolecular Substances / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D008561:Membrane Fusion / Q000276:immunology; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D011817:Rabbits
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000939:Epitopes; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D007074:Immunoglobulin G; D008081:Liposomes; D046911:Macromolecular Substances; D010455:Peptides