Human immunodeficiency virus type 1 envelope glycoprotein 120 V3 glycan supersite (V3 glycan supersite)

The HIV-1 Env gp120 V3 glycan supersite is a critical region of vulnerability on the surface of the HIV-1 envelope spike, primarily defined by the conserved Gly-Asp-Ile-Arg (GDIR) peptide motif and the N332-linked glycan (Sok et al., 2016, Science). This epitope is a primary target for several potent broadly neutralizing antibodies (bNAbs), such as PGT121 and 10-1074, which recognize both the protein backbone and the surrounding carbohydrate shield (Mouquet et al., 2012, PNAS). Biologically, the V3 loop is essential for viral entry as it mediates the interaction with host cell coreceptors CCR5 or CXCR4 (Hwang et al., 1991, Science). In the context of HIV-1 infection, this site is often protected by a dense glycan canopy to evade immune detection, yet the GDIR motif remains a relatively stable target for therapeutic intervention (Stewart-Jones et al., 2016, Cell). Therapeutic strategies targeting this epitope involve the administration of passive bNAbs or the design of vaccines aimed at eliciting similar antibody responses. Clinical trials have demonstrated that antibodies targeting this site, such as 10-1074, can significantly reduce viral loads in infected individuals (Caskey et al., 2017, Nature Medicine). However, the high mutation rate of HIV-1 can lead to the loss of the N332 glycan or alterations in the GDIR motif, resulting in viral escape and therapeutic resistance (Wagh et al., 2018, PLOS Pathogens).

Other names

HIV-1 gp120 V3 glycan / GDIR motif epitopeN332-dependent epitopeGDIR motifgp120 V3 loop baseMan9 glycan patchC3-V3 epitope

Broadly neutralizing antibodies bind to the V3 glycan supersite, which includes the conserved GDIR peptide motif and associated N-linked glycans (primarily N332), thereby blocking viral attachment to coreceptors (CCR5 or CXCR4) and preventing fusion with the host cell membrane (Sok et al., 2016, Science; Mouquet et al., 2012, PNAS).