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

The HIV-1 gp120 CD4-induced (CD4i) epitope is a highly conserved region on the viral envelope glycoprotein gp120 that becomes accessible only after the virus binds to the host cell's CD4 receptor (Kwong et al., 1998, Nature). This binding triggers a conformational change that forms and exposes the bridging sheet, a structural element crucial for the subsequent interaction with co-receptors CCR5 or CXCR4 (Rizzuto et al., 1998, Science). This interaction is a mandatory step for viral-cell membrane fusion and the entry of the viral genome into the host cell (UniProt P04578). Because the CD4i epitope is essential for infection and relatively conserved across diverse HIV-1 strains, it represents a key target for neutralizing antibodies and entry inhibitors (NIH, 2023). However, the epitope is sterically shielded and only transiently exposed during the entry process, which limits the effectiveness of many antibodies targeting this site (Chen et al., 2013, Science). Experimental antibodies such as 17b and 48d have been used extensively to study this site and serve as templates for drug design (PubMed, 2021).

Other names

CD4-induced epitopeCD4i epitopegp120 co-receptor binding sitegp120 CoRBSBridging sheet

Blocking the interaction between the HIV-1 gp120 glycoprotein and host cell co-receptors (CCR5 or CXCR4) to prevent viral entry.