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

The HIV-1 gp120 CD4-induced (CD4i) epitope is a highly conserved, functional region on the viral envelope glycoprotein gp120 that becomes accessible only after the virus binds to the host CD4 receptor (1.1.1, 1.2.2). This binding event triggers a major conformational change, involving the movement of the V1/V2 variable loops and the formation of a four-stranded bridging sheet, which reveals the binding site for the co-receptors CCR5 or CXCR4 (1.2.1, 1.4.5). Because this site is essential for viral entry and is relatively conserved across diverse HIV-1 strains, it represents a critical vulnerability and a primary target for neutralizing antibodies and vaccine development (1.2.4, 1.4.3). However, the epitope is naturally sequestered and sterically shielded, making it difficult for full-sized antibodies to access during the narrow window between CD4 binding and membrane fusion (1.3.1, 1.4.1). Therapeutic strategies include the use of small-molecule CD4 mimics to prematurely expose the site or the development of vaccines, such as the full-length single-chain (FLSC) construct, to elicit broadly reactive anti-CD4i antibodies (1.3.4, 1.5.2). These antibodies can inhibit infection by blocking co-receptor engagement or by mediating antibody-dependent cellular cytotoxicity (ADCC) against infected cells (1.1.2, 1.5.2).

Other names

CD4-induced epitopeCD4i epitopeCo-receptor binding site (CoRBS) epitopeBridging sheet epitopegp120 co-receptor binding site

Inhibition of co-receptor binding, premature triggering of conformational changes, and induction of antibody-dependent cellular cytotoxicity (ADCC).