HIV-1 envelope glycoprotein gp120 CD4-induced epitope (gp120 CD4i epitope)

The HIV-1 Envelope glycoprotein gp120 CD4-induced (CD4i) epitope is a highly conserved region of the viral envelope that becomes accessible only after the gp120 protein binds to the host cell's CD4 receptor (Kwong et al., 1998, Nature). This conformational change exposes the coreceptor binding site (CoRBS), which is essential for the virus to interact with CCR5 or CXCR4 and subsequently trigger membrane fusion and viral entry (Wu et al., 1996, Nature). The m36-like epitope specifically refers to the binding site of the m36 human domain antibody, a potent inhibitor that targets this site with high affinity across diverse HIV-1 clades (Chen et al., 2008, PNAS). Because this epitope is transiently exposed and often sterically shielded by the V1/V2 and V3 loops, it represents a challenging but high-value target for the development of potent entry inhibitors and neutralizing antibodies (Zhang et al., 2010, Journal of Virology). Targeting this site is a key strategy in HIV-1 therapeutics and vaccine design to prevent the progression to AIDS by blocking the transition from CD4 binding to coreceptor engagement.

Other names

CD4-induced epitopeCD4i epitopem36-like epitopegp120 coreceptor binding siteCoRBSHIV-1 gp120 bridging sheet

The mechanism involves the steric blockade of the HIV-1 coreceptor binding site on gp120. Upon CD4 binding, gp120 undergoes a conformational shift that reveals the CD4i epitope; drugs or antibodies targeting this m36-like site prevent the subsequent interaction with CCR5 or CXCR4 coreceptors, thereby halting the viral fusion process (Chen et al., 2008, PNAS; Zhang et al., 2010, Journal of Virology).