Human immunodeficiency virus type 1 envelope glycoprotein trimer (HIV-1 Env trimer) (HIV-1 Env trimer)

The Human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer is the sole viral protein displayed on the surface of HIV-1 virions and is the mediator of viral entry into host cells (UniProt: P04578). It is synthesized as a gp160 precursor that is cleaved by host furin-like proteases into the surface subunit gp120 and the transmembrane subunit gp41, which non-covalently assemble into a heterotrimeric spike (Julien et al., Science, 2013). The trimer functions by binding to the host CD4 receptor and a co-receptor (CCR5 or CXCR4), triggering a massive conformational change that leads to the fusion of the viral and host cell membranes (Kwong et al., Nature, 1998). As the only target for neutralizing antibodies, the Env trimer is the primary focus of HIV-1 vaccine design and passive immunotherapy strategies. Modern therapeutic approaches utilize combinations of broadly neutralizing antibodies (bNAbs) that target distinct conserved regions, such as the CD4 binding site, the V1/V2 apex, the V3 glycan patch, and the membrane-proximal external region (MPER), to overcome the virus's high mutation rate and glycan shielding (Sok and Burton, Nat Rev Rheumatol, 2018). These combined mAb interactions are designed to provide synergistic neutralization and prevent the emergence of escape mutants, which is a significant challenge in treating chronic HIV-1 infection (Bar-On et al., Nature Medicine, 2018).

Other names

gp160gp120/gp41 complexHIV-1 Envelope proteinEnv spikegp140HIV-1 Env

Neutralization of viral particles by blocking CD4 binding sites, inhibiting co-receptor interactions, or preventing the conformational changes required for membrane fusion; often administered in combinations to overcome viral diversity and prevent mutational escape.