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

The HIV-1 clade B envelope glycoprotein (Env) is a trimeric complex essential for viral entry, consisting of three gp120 surface subunits and three gp41 transmembrane subunits (UniProt: P04578). It is synthesized as a gp160 precursor that is proteolytically cleaved by host cell furin-like proteases before being transported to the viral surface (PubMed: 25533458). Env's primary role is to mediate infection by binding to the host CD4 receptor and a coreceptor (CCR5 or CXCR4), triggering a series of conformational changes that lead to the fusion of viral and host cell membranes (NIH: NIAID HIV/AIDS). In Clade B HIV-1, which is the dominant subtype in North America and Europe, Env is a major target for therapeutic intervention, including entry inhibitors like fostemsavir, which binds gp120, and enfuvirtide, which targets gp41 (FDA: Rukobia, Fuzeon). Additionally, it is the sole target for neutralizing antibodies, making it the central focus of HIV vaccine development and broadly neutralizing antibody (bNAb) therapies (PubMed: 30212447). However, the protein's high mutation rate and dense "glycan shield" allow the virus to frequently evade immune detection and develop drug resistance (PubMed: 29133454).

Other names

gp160gp120/gp41 complexEnvEnvelope glycoproteinHIV-1 EnvSurface glycoprotein gp120Transmembrane glycoprotein gp41

Inhibition of viral entry by blocking gp120 attachment to host CD4 receptors or preventing gp41-mediated fusion of viral and cellular membranes (PubMed: 29483515, FDA: Fuzeon).