HIV-1 envelope glycoprotein gp120 V3 region (V3 loop)

The HIV-1 envelope glycoprotein gp120 V3 region, commonly known as the V3 loop, is a highly variable, disulfide-bonded structure that plays a central role in viral entry (1.2.2, 1.3.5). It is the primary determinant of HIV-1 coreceptor tropism, mediating the interaction between the virus and host cell coreceptors, typically CCR5 or CXCR4, after the initial binding of gp120 to CD4 (1.1.1, 1.2.5). This interaction triggers conformational changes in the envelope trimer that lead to membrane fusion and viral entry (1.2.1, 1.2.4). Due to its essential function and accessibility on the viral surface during the entry process, the V3 region is a major target for the host immune response and a key focus for the development of broadly neutralizing antibodies (bnAbs) and vaccines (1.2.2, 1.2.5). However, the high rate of mutation in this region allows the virus to rapidly evolve escape mutants, and the presence of a dense glycan shield can further protect it from antibody recognition (1.2.1, 1.3.5). Therapeutic strategies targeting the V3 region, such as V3-glycan-specific bnAbs like PGT121 and 10-1074, aim to block coreceptor engagement and neutralize a wide range of viral strains (1.2.5, 1.3.2).

Other names

V3 loopThird variable loopV3 domainPrincipal neutralizing determinantPND

Directly binding to the V3 loop or the associated V3-glycan patch on the HIV-1 gp120 protein to sterically block the interaction with host coreceptors (CCR5 or CXCR4), thereby preventing viral-host membrane fusion and entry.