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

The HIV-1 envelope glycoprotein V3 glycan supersite is a major site of vulnerability located at the base of the third variable (V3) loop of the gp120 subunit. It is characterized by a dense cluster of high-mannose glycans, most notably the N332 glycan, and a highly conserved underlying peptide motif known as GDIR (residues 324-327). This supersite is a primary target for several potent broadly neutralizing antibodies (bNAbs) that penetrate the viral glycan shield to bind both the carbohydrate and protein components. Biologically, this region is essential for viral entry as it facilitates the interaction between the HIV-1 envelope and host cell co-receptors, such as CCR5 or CXCR4. Therapeutic interventions, including passive immunization with bNAbs, target this site to neutralize the virus and prevent infection. However, the site is subject to therapeutic challenges such as viral escape through glycan shifting or mutations within the GDIR motif that confer resistance to specific antibodies.

Other names

GDIR motif324GDIR327 motifIR327 motifN332-supersiteV3 loop baseHigh-mannose patch

Broadly neutralizing antibodies bind to the V3 glycan supersite, specifically interacting with the N332 glycan and the conserved GDIR peptide motif, which sterically hinders the envelope glycoprotein from interacting with host co-receptors (CCR5 or CXCR4), thereby blocking viral entry and membrane fusion.