Human immunodeficiency virus type 1 envelope glycoprotein gp120 C1 region (HIV-1 gp120 C1)

The C1 region of the Human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 is a highly conserved N-terminal domain that plays a critical role in the structural organization of the viral envelope trimer and its non-covalent association with the gp41 subunit (Wyatt & Sodroski, 1998). In the native, pre-fusion state of the virus, the C1 region is largely sequestered within the trimer interface, making it inaccessible to most antibodies. However, upon binding to the host cell CD4 receptor, gp120 undergoes significant conformational changes that expose CD4-induced epitopes within the C1 region (Finzi et al., 2012). These exposed epitopes are major targets for non-neutralizing antibodies, such as A32 and C11, which facilitate the elimination of infected cells through antibody-dependent cellular cytotoxicity (ADCC) (Pollara et al., 2011). The importance of C1-specific immune responses was underscored by the RV144 vaccine trial, where ADCC-mediating antibodies targeting the C1 and V1V2 regions were identified as potential correlates of reduced infection risk (Bonsignori et al., 2012). Consequently, the C1 region is a focal point for the development of Shock and Kill strategies and next-generation vaccines aimed at enhancing Fc-mediated effector functions against HIV-1.

Other names

gp120 C1 domainHIV-1 gp120 constant region 1N-terminal region of gp120C1-C2 conformational epitopesA32-like epitopes

Induction of antibody-dependent cellular cytotoxicity (ADCC) against HIV-infected cells and stabilization of the envelope glycoprotein in an open conformation to expose vulnerable epitopes.