CD4 binding site of HIV-1 envelope glycoprotein gp120 (CD4bs)

The **CD4 binding site of HIV-1 envelope glycoprotein gp120 (CD4bs)** is a conformational epitope located on the gp120 subunit of the HIV envelope trimer, formed after proteolytic cleavage of the gp160 precursor into gp120 (surface subunit) and gp41 (transmembrane subunit)[2][7][8]. This site is responsible for high-affinity binding of HIV-1 to the **CD4 receptor** on host T cells, acting as the primary determinant of viral attachment and a trigger for subsequent viral entry processes[1][8]. After CD4 engagement, gp120 undergoes structural rearrangement that exposes or creates a binding site for a chemokine coreceptor (CCR5 or CXCR4), ultimately enabling gp41 to mediate membrane fusion[2][5][8]. The CD4bs is a major target for **broadly neutralizing antibodies** in natural infection and vaccine research[1][4][5]. It is an attractive but challenging therapeutic target due to its partial occlusion on native Env trimers and propensity for immune evasion through glycosylation and sequence variation[4][5].

Other names

CD4bsHIV-1 envelope CD4 binding siteHIV-1 gp120 CD4 binding siteHIV Env CD4 binding site

Antibody-mediated viral neutralization by blocking gp120-CD4 interaction; Inhibition of HIV-1 entry into host cell by receptor blockade