Human immunodeficiency virus 1 envelope glycoprotein gp120 V2 loop (V2 loop) (V2 loop)

The HIV-1 gp120 V2 loop epitopes are critical regions on the surface of the Human Immunodeficiency Virus type 1 (HIV-1) envelope glycoprotein (Env) (NIH, 2023; ACS, 2023). Located at the apex of the trimeric Env spike, the V2 loop (often as part of the V1V2 domain) plays a dual role in viral pathogenesis: it stabilizes the pre-fusion trimer and shields conserved regions like the CD4 binding site and V3 loop from the host immune system (NIH, 2014; NIH, 2023). Furthermore, the V2 loop contains a motif that interacts with the alpha-4 beta-7 integrin, facilitating the homing of the virus to gut-associated lymphoid tissues, which are primary sites of early viral replication (PNAS, 2020; NIH, 2023). Broadly neutralizing antibodies (bNAbs) such as PG9 and PGT145 target conformational epitopes in this region, often involving the N160 glycan, to potently inhibit viral entry across diverse HIV-1 strains (NIH, 2023; MDPI, 2024). The importance of V2-directed immunity was underscored by the RV144 vaccine trial, where antibodies to the V2 loop were identified as a primary correlate of protection against HIV-1 acquisition (NIH, 2014; NIH, 2023). Despite its potential as a therapeutic and prophylactic target, the high sequence variability and dense glycosylation of the V2 loop pose significant challenges for the development of universal vaccines and long-acting therapies (NIH, 2023; ResearchGate, 2006).

Other names

V1V2 apexV2 domainV1V2 loopV2i epitopesV2q epitopesV2p epitopes

Neutralization of HIV-1 by blocking viral attachment to host receptors (CD4 and alpha-4 beta-7 integrin), destabilizing the envelope trimer, and preventing the conformational changes required for membrane fusion.