Neutralizing Antibodies Targeting HIV-1 gp41
Open Access
- 23 October 2020
- Vol. 12 (11), 1210
- https://doi.org/10.3390/v12111210
Abstract
HIV-1 vaccine research has obtained an enormous boost since the discovery of many broadly neutralizing antibodies (bnAbs) targeting all accessible sites on the HIV-1 envelope glycoprotein (Env). This in turn facilitated high-resolution structures of the Env glycoprotein in complex with bnAbs. Here we focus on gp41, its highly conserved heptad repeat region 1 (HR1), the fusion peptide (FP) and the membrane-proximal external region (MPER). Notably, the broadest neutralizing antibodies target MPER. Both gp41 HR1 and MPER are only fully accessible once receptor-induced conformational changes have taken place, although some studies suggest access to MPER in the close to native Env conformation. We summarize the data on the structure and function of neutralizing antibodies targeting gp41 HR1, FP and MPER and we review their access to Env and their complex formation with gp41 HR1, MPER peptides and FP within native Env. We further discuss MPER bnAb binding to lipids and the role of somatic mutations in recognizing a bipartite epitope composed of the conserved MPER sequence and membrane components. The problematic of gp41 HR1 access and MPER bnAb auto- and polyreactivity is developed in the light of inducing such antibodies by vaccination.Keywords
This publication has 154 references indexed in Scilit:
- Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9Nature, 2011
- Structural Characterization of HIV gp41 with the Membrane-proximal External RegionOnline Journal of Public Health Informatics, 2010
- Prolonged exposure of the HIV-1 gp41 membrane proximal region with L669S substitutionProceedings of the National Academy of Sciences of the United States of America, 2010
- Aromatic residues at the edge of the antibody combining site facilitate viral glycoprotein recognition through membrane interactionsProceedings of the National Academy of Sciences of the United States of America, 2010
- Role of HIV membrane in neutralization by two broadly neutralizing antibodiesProceedings of the National Academy of Sciences of the United States of America, 2009
- Affinity maturation by targeted diversification of the CDR-H2 loop of a monoclonal Fab derived from a synthetic naïve human antibody library and directed against the internal trimeric coiled-coil of gp41 yields a set of Fabs with improved HIV-1 neutralization potency and breadthVirology, 2009
- Viral membrane fusionNature Structural & Molecular Biology, 2008
- A fusion-intermediate state of HIV-1 gp41 targeted by broadly neutralizing antibodiesProceedings of the National Academy of Sciences of the United States of America, 2008
- Structural definition of a conserved neutralization epitope on HIV-1 gp120Nature, 2007
- Structural basis for HIV-1 neutralization by a gp41 fusion intermediate–directed antibodyNature Structural & Molecular Biology, 2006