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

The CD4-induced epitope on HIV-1 envelope glycoprotein gp120, often called the CD4i epitope, emerges on the gp120 subunit of the Env trimer upon binding to the host CD4 receptor. This conformational change rearranges gp120, forming a bridging sheet structure that exposes the epitope, which overlaps with the coreceptor (CCR5 or CXCR4) binding site, enabling subsequent viral-host membrane fusion for HIV entry. In the unliganded state, gp120 conceals this site via V1/V2 and V3 loops; CD4 binding displaces V1/V2 by ~40 Å, rotates gp120 protomers, and unmasks the epitope for immune recognition or coreceptor access. This epitope serves as a key target for broadly neutralizing antibodies like 17b and 21c, which mimic coreceptors to block infection, informing HIV vaccine and therapeutic designs despite Env's high variability and glycan shielding. Its role underscores HIV's evasion strategies, where flexibility hinders consistent antibody elicitation.

Other names

CD4-induced (CD4i) antibody epitopecoreceptor-binding site-overlapping epitope17b epitopebridging sheet epitope

Antibody binding to exposed epitope post-CD4 engagement, blocking coreceptor binding and fusion