Human immunodeficiency virus 1 envelope glycoprotein gp140 (HIV-1 gp140)

The **human immunodeficiency virus 1 envelope glycoprotein gp140** is a recombinant, soluble ectodomain of the HIV-1 envelope spike, comprising the gp120 and the external portion of the gp41 subunits but lacking the transmembrane and cytoplasmic tail domains. In viral biology, the native envelope spike is a trimer of gp120–gp41 heterodimers assembled from a gp160 precursor and is essential for viral entry into host cells: gp120 mediates binding to cellular CD4 and chemokine receptors (CCR5 or CXCR4), triggering gp41 to undergo conformational changes that drive fusion between the viral and host cell membranes. gp140 constructs, particularly stabilized trimers (e.g., SOSIP gp140), are extensively used as vaccine immunogens due to their ability to structurally and antigenically mimic the native envelope spike and present neutralization-sensitive epitopes. They are principal targets for broadly neutralizing antibodies and underlie most current HIV-1 vaccine strategies. However, the high variability and heavy glycosylation of HIV-1 Env challenge both vaccine and therapeutic antibody development, making gp140 a centerpiece of complex immunological and pharmacological research.

Other names

HIV-1 envelope glycoprotein gp140gp140Trimeric HIV-1 Env ectodomain (contextual)HIV-1 Env (when referring to the whole spike, but “gp140” generally refers to the soluble ectodomain)

Entry/Fusion inhibition: Agents (e.g., enfuvirtide) block conformational changes in the gp41 subunit, preventing membrane fusion; Neutralization: Broadly neutralizing antibodies bind to conformational or glycan-dependent epitopes on gp120/gp41, blocking viral attachment, receptor engagement, or fusion; Blockade of receptor interaction: Some drugs/antibodies hinder binding to CD4 or co-receptors, thereby blocking viral entry.