HIV-1 Envelope glycoprotein V3 glycan and related non-CD4 binding site epitopes (HIV-1 Env V3 glycan/non-CD4bs)

The HIV-1 Envelope glycoprotein (Env) V3 glycan supersite and related non-CD4 binding site (non-CD4bs) epitopes are critical regions of vulnerability on the viral spike targeted by broadly neutralizing antibodies (bNAbs) (Sok et al., 2014, Science). The V3 glycan supersite is defined by a conserved cluster of high-mannose glycans, particularly at position N332, and the base of the V3 loop on the gp120 subunit (Kong et al., 2016, Nat Commun). Other related non-CD4bs epitopes include the V1/V2 apex, the gp120-gp41 interface, and the membrane-proximal external region (MPER), all of which are essential for the structural integrity and fusion function of the Env trimer (Burton & Hangartner, 2016, Annu Rev Immunol). Biologically, these sites facilitate the transition of the Env protein from a pre-fusion to a post-fusion state during viral entry into host CD4+ T cells (NIH, 2023). In HIV-1 infection, these epitopes are often shielded by a dense glycan shield to prevent immune recognition. Therapeutic strategies involve the passive transfer of bNAbs like 10-1074 or PGT121, which can potently neutralize diverse viral strains by blocking coreceptor binding or fusion (Caskey et al., 2017, Nature). These sites are also primary focuses for structure-based vaccine design aimed at inducing long-lasting protective immunity.

Other names

V3 glycan supersiteN332-dependent epitopegp120 V3 loop glycanHIV-1 Env V3-baseNon-CD4bs neutralizing epitopesV3 glycan patchV3 glycan-dependent epitope

Broadly neutralizing antibodies (bNAbs) bind to the V3 glycan supersite or related non-CD4bs epitopes, sterically hindering coreceptor (CCR5/CXCR4) binding or preventing the conformational changes in the envelope trimer required for viral-host membrane fusion (Sok et al., 2014, Science; Garces et al., 2015, Immunity).