HIV-1 group M envelope glycoprotein (HIV-1 Env)

The HIV-1 group M envelope glycoprotein (Env) is the sole viral protein displayed on the surface of the HIV-1 virion, making it the primary target for neutralizing antibodies and a central focus for vaccine design (UniProt P04578). It is synthesized as a gp160 precursor that is subsequently cleaved by host proteases into the surface subunit gp120 and the transmembrane subunit gp41, which assemble into a non-covalent trimeric spike (PubMed: 28431251). Env mediates viral entry by binding to the host CD4 receptor and a co-receptor (CCR5 or CXCR4), triggering a series of conformational changes that lead to the fusion of viral and host cell membranes (NIH: HIV/AIDS Glossary). Therapeutic strategies targeting Env include attachment inhibitors like Fostemsavir, which binds gp120, and fusion inhibitors like Enfuvirtide, which targets gp41 (PubChem CID 46830666). Additionally, broadly neutralizing antibodies (bNAbs) such as VRC01 and PGT121 target conserved epitopes on Env to prevent infection across diverse viral strains (PubMed: 30212447). However, the target presents significant challenges due to its high sequence variability, extensive glycosylation (the glycan shield), and the ability to rapidly evolve escape mutations (PubMed: 25329758).

Other names

gp160gp120/gp41 complexHIV-1 surface glycoproteinEnvelope spikeEnv polyprotein

Inhibition of viral attachment to CD4 receptors, blockade of co-receptor binding, and prevention of gp41-mediated membrane fusion.