HIV-1 envelope glycoprotein gp120 V3 glycan supersite (gp120 V3 glycan supersite)

The HIV-1 envelope glycoprotein gp120 V3 glycan supersite is a highly conserved region on the outer domain of the gp120 subunit, characterized by a dense cluster of oligomannose-type glycans centered around the asparagine at position 332 (N332). This "supersite of vulnerability" is a primary target for some of the most potent broadly neutralizing antibodies (bNAbs) identified to date, such as PGT121 and 10-1074. Biologically, the site is involved in the initial stages of viral entry, where the V3 loop interacts with host co-receptors like CCR5 or CXCR4 after CD4 binding. The dense glycan shield normally serves to protect the virus from immune recognition, but bNAbs have evolved to penetrate this shield and bind both the glycans and the underlying conserved protein motifs, such as the GDIR peptide motif. In clinical settings, targeting this supersite with passive administration of bNAbs has shown promise in suppressing viral load and preventing infection in both animal models and human trials. However, the virus can escape through mutations that shift or remove glycosylation sites, necessitating the use of combination therapies. This site is also a major focus for HIV-1 vaccine design, as immunogens that can elicit antibodies against this supersite could provide broad protection against diverse viral strains. Despite its potential, the complexity of the glycan-protein interface remains a significant challenge for the development of effective vaccines and long-acting therapeutics.

Other names

N332-glycan supersiteV3-glycan patchIntrinsic mannose patch (IMP)N332 supersiteV3/N332 glycan siteBase of the V3 loop

Neutralization of HIV-1 by binding to the V3 glycan supersite, which blocks the interaction of gp120 with host cell receptors (CD4 and co-receptors CCR5/CXCR4) and prevents viral fusion and entry into host cells.