Human immunodeficiency virus 1 envelope glycoprotein V3-glycan supersite (HIV-1 Env V3-glycan supersite)

The HIV-1 Env N156 glycan and V3 loop base region represent a critical vulnerable epitope on the HIV-1 envelope glycoprotein (gp120), collectively known as the V3-glycan supersite (Sok et al., 2014, Science). This site is defined by a cluster of conserved N-linked glycans, most notably at positions N332 and N156, which serve as the primary recognition elements for several potent broadly neutralizing antibodies (bNAbs) including PGT121, 10-1074, and PGT128 (Mouquet et al., 2012, PNAS). Although the N156 glycan is located within the V1/V2 loop, it is positioned in close spatial proximity to the base of the V3 loop in the prefusion closed conformation of the Env trimer, forming a complex glycan-protein surface (Garces et al., 2015, Immunity). This region is a major focus for therapeutic intervention and vaccine design because antibodies targeting it can neutralize a vast majority of global HIV-1 isolates by preventing the virus from binding to host receptors and undergoing the conformational changes necessary for membrane fusion (Julien et al., 2013, Science). Clinical trials using bNAbs that target this site have demonstrated significant, albeit transient, reductions in viral load, highlighting its importance as a therapeutic target (Caskey et al., 2017, Nature).

Other names

V3-glycan patchN332-glycan supersitePGT121 epitope10-1074 epitopeHIV-1 gp120 V3 loop base region

Broadly neutralizing antibodies (bNAbs) bind to the V3-glycan supersite, which includes the N156 glycan and the base of the V3 loop, to sterically block the envelope trimer from interacting with the CD4 receptor and coreceptors (CCR5/CXCR4), thereby inhibiting viral entry and membrane fusion (Julien et al., 2013, Science; Sok et al., 2014, Science).