HIV-1 envelope glycoprotein fusion peptide and gp120 N88 glycan epitope (HIV-1 Env FP-N88 epitope)

The HIV-1 gp41 fusion peptide (FP) and the adjacent gp120 N88 glycan constitute a critical site of vulnerability on the HIV-1 envelope (Env) trimer (Kong et al., 2016, Science). The FP is a highly conserved, hydrophobic sequence at the N-terminus of gp41 that inserts into the host cell membrane to initiate fusion (Zhou et al., 2022, Nature Communications). Antibodies like VRC34.01 target this region by binding to the N-terminal residues of the FP while also interacting with the N88 glycan on the gp120 subunit (Xu et al., 2018, Immunity). This dual interaction stabilizes the antibody-Env complex and blocks the conformational changes required for viral entry. Because the FP is relatively conserved across different HIV-1 strains, this epitope is a primary focus for the development of broadly neutralizing antibodies and structure-based vaccine design (Dingens et al., 2018, Journal of Virology).

Other names

gp41 fusion peptide epitopeFP-directed epitopeVRC34.01 epitopeHIV-1 Env fusion peptide siteN88-glycan-dependent epitope

Neutralization of HIV-1 by binding to the N-terminal fusion peptide of gp41 and the N88 glycan of gp120, thereby sterically hindering the insertion of the fusion peptide into the host cell membrane and preventing viral-host membrane fusion (Kong et al., 2016, Science).