HIV-1 envelope glycoprotein gp120 (gp120) (gp120)

The HIV-1 envelope glycoprotein gp120 is a surface subunit of the viral envelope spike (Env) that is essential for the virus's ability to infect host CD4+ T cells (UniProt P04578). It functions by binding to the host CD4 receptor, which induces conformational changes that allow for subsequent binding to co-receptors (CCR5 or CXCR4) and eventual membrane fusion (PubMed: 17712420). The CD4-binding site (CD4bs) on gp120 is a highly conserved and functionally critical region, making it a primary target for therapeutic intervention and vaccine design. The b12 antibody is a well-characterized broadly neutralizing antibody (bnAb) that targets this CD4bs; its paratope—the specific part of the antibody that recognizes the antigen—mimics the CD4 receptor's interaction with gp120 (PubMed: 11449270). While gp120 is a major target for drugs like the attachment inhibitor fostemsavir, the protein's extreme genetic diversity and extensive glycosylation present significant challenges for achieving broad and durable clinical efficacy (PubMed: 30135522). Therapeutic strategies focusing on this target must account for the rapid emergence of resistance mutations and the structural masking of vulnerable epitopes.

Other names

gp120Envelope surface glycoprotein gp120EnvCD4-binding siteParatope of b12 broadly neutralizing antibody

Inhibition of viral entry by blocking the interaction between the HIV-1 gp120 subunit and the host CD4 receptor.