Human immunodeficiency virus type 1 envelope glycoprotein 120 CD4-induced epitope (HIV-1 gp120 CD4i epitope)

The HIV-1 envelope glycoprotein 120 (gp120) CD4-induced (CD4i) epitope is a highly conserved, functional region of the viral surface protein that is essential for host cell entry (Kwong et al., 1998). This epitope is sequestered in the native, unliganded state of the HIV-1 envelope trimer and only becomes exposed or formed following the binding of gp120 to the primary host receptor, CD4. The resulting conformational change leads to the formation of a four-stranded beta-sheet known as the "bridging sheet" and the repositioning of the V3 loop, which together constitute the binding site for the co-receptors CCR5 or CXCR4 (Rizzuto et al., 1998). Because the CD4i epitope is critical for co-receptor recruitment and subsequent membrane fusion, it is a major target for neutralizing antibodies and entry inhibitors. However, its transient exposure and the steric hindrance provided by the surrounding viral and cellular membranes pose significant challenges for therapeutic intervention. Current research focuses on using CD4-mimetic compounds to stabilize this "open" conformation, thereby sensitizing the virus to neutralization by CD4i-specific antibodies and facilitating antibody-dependent cellular cytotoxicity (ADCC) (Veillette et al., 2014; Haim et al., 2009).

Other names

CD4-induced epitopeCD4i epitopeCo-receptor binding siteCoRBSgp120 bridging sheetCD4-induced co-receptor-proximal epitope

Inhibition of viral entry by blocking the interaction between the gp120 bridging sheet and host co-receptors CCR5 or CXCR4.