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

The HIV-1 envelope protein V3 glycan supersite is a highly conserved and potent antigenic region located on the gp120 subunit of the viral envelope trimer (Sok et al., 2014, Science). It is defined by its reliance on the asparagine-linked glycan at position 332 (N332) and the surrounding protein architecture at the base of the V3 loop (Mouquet et al., 2012, PNAS). This site is the primary target for a class of broadly neutralizing antibodies (bNAbs), including PGT121 and 10-1074, which are currently being evaluated in clinical trials for both HIV-1 prevention and therapy (Caskey et al., 2017, Nature). Biologically, the V3 loop plays a crucial role in viral pathogenesis by mediating the interaction between the virus and host cell co-receptors, such as CCR5 or CXCR4, which is a prerequisite for membrane fusion (Sok et al., 2016, Science Translational Medicine). In the context of disease, the V3 glycan supersite represents a vulnerability site because antibodies targeting it can neutralize a wide range of global HIV-1 isolates (Wagh et al., 2018, PLOS Pathogens). Drugs targeting this supersite work by sterically hindering the envelope's ability to bind to host cells, thereby preventing the infection of new CD4+ T lymphocytes. However, the high genetic diversity of HIV-1 allows the virus to escape neutralization through mutations that shift or remove the N332 glycan, necessitating the use of combination bNAb regimens (Gilead Sciences, 2023). Overall, this target is central to the development of next-generation HIV-1 biologics and vaccine strategies aimed at eliciting broad protection.

Other names

N332 glycan supersiteV3-base glycan patchPGT121-class epitope10-1074-class epitopegp120 V3 glycan site

Broadly neutralizing antibodies (bNAbs) target the V3 glycan supersite by binding to a complex epitope composed of the N332 glycan and the conserved protein base of the V3 loop. This binding prevents the HIV-1 envelope trimer from interacting with host co-receptors (CCR5 or CXCR4), which effectively blocks the conformational changes required for viral-host membrane fusion and subsequent viral entry into the host cell (Mouquet et al., 2012, PNAS; Sok et al., 2014, Science).