HIV-1 gp120 V3-glycan region [1, 8, 13] (V3-glycan [2, 3, 9])

The HIV-1 gp120 V3-glycan region is a major site of vulnerability on the HIV-1 envelope glycoprotein (Env) trimer, primarily located at the base of the third variable (V3) loop [1, 3]. This region is characterized by a dense cluster of high-mannose N-linked glycans, most notably the highly conserved glycan at position N332, which forms the core of what is often called the "N332-glycan supersite" [7, 13]. Biologically, the V3 loop is essential for viral entry as it mediates the interaction with host coreceptors (CCR5 or CXCR4) following CD4 binding [14]. While the "glycan shield" typically protects the virus from immune recognition, the V3-glycan region is a key target for a class of potent broadly neutralizing antibodies (bNAbs) such as PGT121 and 10-1074 [1, 4, 9]. These antibodies penetrate the glycan shield to contact both the conserved protein motifs, such as the GDIR motif, and the associated glycans, effectively blocking viral entry and neutralizing a wide range of HIV-1 variants [9, 15]. This target is a primary focus for passive immunotherapy and the design of next-generation HIV vaccines aimed at eliciting broad and potent humoral immunity [7, 16]. Therapeutic challenges include viral escape through glycan shifting and the high degree of glycan heterogeneity across different viral strains [3, 4, 18]. Despite these challenges, targeting this region remains one of the most promising strategies for achieving long-term control or prevention of HIV-1 infection [5, 10].

Other names

V3-glycan supersite [5, 7, 16]N332-glycan supersite [7, 13, 17]V3-glycan patch [1, 13]Intrinsic mannose patch [13]N332-directed epitope [2, 10, 15]

Neutralization of HIV-1 by blocking viral entry and coreceptor binding [3, 4, 14].