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

The HIV-1 envelope glycoprotein (Env) V3 glycan supersite is a major target for broadly neutralizing antibodies (bNAbs) located on the gp120 subunit of the prefusion Env trimer (Sok et al., 2016, Science). This site is defined by a cluster of conserved N-linked glycans, primarily centered around the N332 glycan, and a highly conserved protein motif known as GDIR (residues 324-327) at the base of the V3 loop (Garces et al., 2015, Immunity). The GDIR motif, particularly the I326 and R327 residues, provides essential protein-antibody contacts that allow bNAbs to bind across diverse viral clades. Biologically, this region is involved in the transition of the Env trimer from a closed to an open state and facilitates interaction with host co-receptors like CCR5 or CXCR4 (Barnes et al., 2018, Nature Communications). In the context of disease, the V3 glycan supersite is a primary focus for HIV-1 vaccine design and passive immunotherapy, as antibodies targeting this site, such as 10-1074 and PGT121, have shown potent neutralizing activity in clinical trials (Caskey et al., 2017, Nature Medicine). However, the virus can escape these antibodies through mutations that shift glycan positions or alter the GDIR motif, presenting a significant challenge for long-term efficacy.

Other names

N332 glycan supersiteGDIR motifgp120 V3 loop baseV3-base supersiteMan9-cluster site

Neutralization of viral entry by sterically blocking co-receptor binding sites and stabilizing the prefusion conformation of the Env trimer.