Cholesterol-Mediated Conformational Plasticity Restrains Immunogenicity and Promotes Membrane Fusion by an HIV Sequence Juxtaposed to the Lipid Envelope

Abstract

HIV-1 fusion of host-cell and viral membranes is induced by the transmembrane subunit gp41 of the envelope glycoprotein (Env). Antibodies targeting the C-terminal sequence of the Membrane-Proximal External Region (C-MPER) exert potent and broad neutralization of HIV-1 by blocking the fusogenic activity of gp41. Thus, recreating the structure that generates broadly neutralizing C-MPER antibodies during infection is a major goal in HIV vaccine development. Here, we have reconstituted peptides that contain the C-MPER epitope and the TMD residues required for the anchorage of the Env glycoprotein in lipid bilayers, and analyzed peptide structure, membrane perturbations and immunogenicity of the resulting Lipid-Peptide Formulations (LPFs).