Human immunodeficiency virus 1 envelope glycoprotein 120 V3-glycan supersite (HIV-1 gp120 V3-glycan supersite) (HIV-1 gp120 V3-glycan supersite)

The HIV-1 Env gp120 V3-glycan supersite is a critical antigenic region on the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer, primarily defined by the conserved N-linked glycan at position N332 and the base of the third variable (V3) loop (Garces et al., 2015, Immunity). This site is essential for viral infectivity as the V3 loop mediates binding to host cell co-receptors, such as CCR5 or CXCR4, following initial CD4 attachment (Sok et al., 2016, Science). It is a primary target for potent broadly neutralizing antibodies (bNAbs) like PGT121 and 10-1074, which are being investigated for both HIV-1 prevention and therapy (Caskey et al., 2017, Nature Medicine). These antibodies recognize a complex epitope consisting of both the protein backbone and high-mannose glycans, effectively blocking the viral entry process. In clinical settings, targeting this supersite has shown promise in reducing plasma viremia, although the high genetic diversity of HIV-1 and the potential for glycan-shifting mutations present significant challenges for sustained efficacy (Wagh et al., 2018, PLOS Pathogens). Furthermore, the site is a focal point for next-generation vaccine design aimed at eliciting similar broadly neutralizing responses in uninfected individuals (Sok et al., 2014, Science).

Other names

V3-glycan patchN332-glycan supersiteV3-base epitopePGT121-class epitopeHigh-mannose patchN332-dependent epitopeV3-base glycan site

Broadly neutralizing antibodies (bNAbs) target the V3-glycan supersite by using long heavy-chain complementarity-determining regions (HCDR3) to penetrate the dense glycan shield and bind to the underlying gp120 protein surface (Pejchal et al., 2011, Science). This binding sterically hinders the V3 loop from interacting with host cell co-receptors (CCR5 or CXCR4), effectively blocking viral attachment and entry (Sok et al., 2016, Science). Additionally, some bNAbs targeting this site can stabilize the envelope trimer in its closed, pre-fusion conformation, preventing the structural rearrangements necessary for membrane fusion with the host cell (Barnes et al., 2018, Nature Communications).