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Conformational Evaluation of HIV-1 Trimeric Envelope Glycoproteins Using a Cell-based ELISA Assay
Published on: September 14, 2014
Recognition of membrane-bound fusion-peptide/MPER complexes by the HIV-1 neutralizing 2F5 antibody: implications for
Nerea Huarte1, Aitziber Araujo, Rocio Arranz
1Biophysics Unit (CSIC-UPV/EHU) and Biochemistry and Molecular Biology Department, University of the Basque Country (UPV/EHU), Bilbao, Spain.
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.
Insights
Researchers found that complexes of the HIV-1 glycoprotein-41 membrane proximal external region (MPER) and fusion peptide (FP) can bind the 2F5 antibody on lipid vesicles. This membrane-bound complex may stabilize the 2F5 epitope for potential anti-HIV vaccine development.
Area of Science:
- Virology
- Immunology
- Structural Biology
Background:
- The membrane proximal external region (MPER) of HIV-1 glycoprotein-41 contains the epitope recognized by the broadly neutralizing antibody 2F5.
- Mimicking this MPER 2F5 epitope is a key strategy for developing anti-HIV vaccines.
- The native folding of the 2F5 epitope may depend on membrane proximity and interactions with other viral components.
Purpose of the Study:
- To investigate the structural basis for 2F5 epitope recognition by antibodies.
- To explore the role of the fusion peptide (FP) in stabilizing the MPER epitope.
- To assess the immunogenicity of MPER:FP complexes as potential vaccine candidates.
Main Methods:
- Formation of oligomeric complexes between MPER and FP peptides.
- Partitioning of MPER:FP complexes into lipid vesicles.
- Cryo-transmission electron microscopy (cryo-TEM) to visualize complexes at lipid bilayer surfaces.
- Immunization of rabbits with MPER:FP peptide-vesicle formulations.
Main Results:
- MPER:FP complexes were shown to partition into lipid vesicles.
- The 2F5 antibody specifically bound to these complexes on the surface of liposomes.
- Cryo-TEM provided structural evidence for antibody recognition at the lipid bilayer interface.
- The MPER:FP-vesicle formulations elicited cross-reactive anti-MPER antibodies in rabbits.
Conclusions:
- Interactions with N-terminal regions, such as the FP, can stabilize the MPER 2F5 epitope.
- The membrane-bound MPER:FP complex presents a potential antigen for anti-HIV vaccine strategies.
- This finding offers structural insights into antibody recognition of viral fusion epitopes.
