HIV-1 envelope glycoprotein gp41 fusion peptide and gp120 N88 glycan epitope (HIV-1 FP-N88 epitope)

The HIV-1 gp41 fusion peptide N-terminal region with adjacent gp120 N88 glycan is a critical site of vulnerability on the HIV-1 envelope (Env) glycoprotein trimer (Kong et al., 2016, Science). The fusion peptide (FP) is a highly conserved, hydrophobic sequence at the N-terminus of the gp41 subunit that mediates the fusion of viral and host cell membranes during entry (Xu et al., 2018, Nature). The N88 glycan, located on the gp120 subunit, is a key structural component that, along with the FP, forms a distinct epitope recognized by broadly neutralizing antibodies (bNAbs) such as VRC34.01 (Zhou et al., 2020, Cell). Binding to this site prevents the FP from inserting into the target cell membrane, effectively neutralizing the virus across a wide range of strains. Because the FP sequence is relatively invariant compared to other regions of the Env protein, it serves as an attractive target for universal vaccine strategies. Therapeutic interventions targeting this region aim to block the conformational changes in the Env trimer that are necessary for viral infection. This epitope is unique because it combines a peptide component with a specific carbohydrate moiety, requiring antibodies to achieve high-affinity interactions with both. Current research focuses on using this site to elicit protective immune responses through protein engineering and nanoparticle-based immunogens (Dingens et al., 2018, PLoS Pathogens).

Other names

gp41 fusion peptide epitopeVRC34 epitopeFP-N88 siteHIV-1 Env fusion peptide N-terminal regionFusion peptide-N88 glycan site

Neutralization of viral entry by binding to the fusion peptide and adjacent glycans, thereby preventing the insertion of the fusion peptide into the host cell membrane and inhibiting the conformational transition of the envelope trimer required for fusion (Kong et al., 2016, Science; Xu et al., 2018, Nature).