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

The Human Immunodeficiency Virus Type 1 (HIV-1) envelope glycoprotein (Env) is a trimeric complex consisting of three gp120 surface subunits and three gp41 transmembrane subunits (UniProt P04578). It is the sole viral protein exposed on the surface of the HIV-1 virion and is essential for viral entry into host cells. Env functions by binding to the host cell CD4 receptor and subsequently to a co-receptor (CCR5 or CXCR4), which triggers a series of conformational changes leading to the fusion of viral and host cell membranes (Ward & Wilson, 2017). Conserved neutralizing epitopes within Env, such as the CD4 binding site (CD4bs), the V3-glycan supersite, and the membrane-proximal external region (MPER), are primary targets for the development of broadly neutralizing antibodies (bNAbs) and entry inhibitors (NIAID, 2023). Therapeutic strategies targeting Env include attachment inhibitors like fostemsavir, which binds gp120, and fusion inhibitors like enfuvirtide, which targets gp41 (ViiV Healthcare, 2020; Roche, 2003). Despite its importance, the high genetic diversity of HIV-1 and the presence of a dense glycan shield on Env pose significant hurdles for vaccine development and long-term drug efficacy.

Other names

gp160gp120/gp41 complexHIV-1 envelope spikesEnv trimerEnvelope glycoprotein gp160

Attachment inhibition by binding to gp120 to prevent CD4 interaction, fusion inhibition by binding to gp41 to prevent membrane fusion, and virus neutralization via antibody-mediated blocking of entry sites (Ward & Wilson, 2017; ViiV Healthcare, 2020).