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

The Human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein 120 (gp120) CD4-induced (CD4i) epitope is a highly conserved region essential for viral entry into host cells (Kwong et al., Nature, 1998). This epitope is typically hidden within the gp120 structure and only becomes accessible after the virus binds to the primary CD4 receptor on T-cells or macrophages (Rizzuto et al., Science, 1998). This binding event triggers a conformational change that forms a 'bridging sheet,' creating the binding site for the viral co-receptors CCR5 or CXCR4 (Chen et al., Science, 2019). Because this site is functionally indispensable and conserved across diverse HIV-1 strains, it is a major target for vaccine design and neutralizing antibodies. Therapeutic approaches often involve using CD4-mimetic compounds to 'prime' the virus by exposing this epitope, making it vulnerable to neutralization by CD4i-specific antibodies like 17b (Haim et al., PLoS Pathogens, 2009). However, the rapid mutation of the virus and the steric shielding provided by the envelope trimer remain significant hurdles for effective drug development. Additionally, the transient nature of the CD4-bound state means that antibodies targeting this epitope must act quickly before fusion occurs. Despite these challenges, the CD4i epitope remains a cornerstone of research into broadly neutralizing antibody responses and HIV-1 entry inhibition.

Other names

CD4i epitopeCD4-induced sitegp120 bridging sheetCo-receptor binding site17b-binding site

Neutralization of viral entry by blocking the interaction between the viral gp120 protein and host co-receptors (CCR5 or CXCR4) following CD4 binding (Kwong et al., 1998; Rizzuto et al., 1998).