HIV-1 envelope glycoprotein gp120 V2 apex epitope (V2 apex)

The HIV-1 Env gp120 V2 apex epitope is a highly conserved, quaternary site located at the top of the trimeric envelope glycoprotein (Env) spike of the Human Immunodeficiency Virus type 1 (HIV-1) (NIH, 2017; MDPI, 2023). This epitope is formed by the association of the first and second variable loops (V1V2) from the three gp120 protomers and is characterized by a dense cluster of N-linked glycans, most notably at position N160, and a lysine-rich strand (NIH, 2011; NIH, 2017). Biologically, the V2 apex plays a critical role in maintaining the stability of the prefusion Env trimer and shielding more conserved regions, such as the V3 loop and the coreceptor binding site, from immune recognition (NIH, 2015; ASM, 2026). It also facilitates viral entry by interacting with host cell receptors like α4β7 integrin (NIH, 2017; MDPI, 2023). As a therapeutic target, the V2 apex is recognized by some of the most potent and broadly neutralizing antibodies (bNAbs), such as PG9, PG16, and CAP256-VRC26.25, which neutralize the virus by locking the trimer in a closed state and preventing the conformational changes necessary for membrane fusion (NIH, 2011; NIH, 2026). Despite its vulnerability, the epitope presents significant challenges for vaccine design due to its high sequence variability in surrounding regions and the requirement for complex glycan-protein interactions for antibody binding (NIH, 2017; MDPI, 2023).

Other names

V1V2 apexTrimer apexV2-glycan apexQuaternary V2 epitopeV2q epitope

Neutralization of HIV-1 by binding to the prefusion trimer apex, stabilizing the closed conformation of the envelope spike, and preventing the conformational changes required for CD4 binding and subsequent membrane fusion (NIH, 2011; ASM, 2026).