Human immunodeficiency virus 1 surface glycoprotein gp120 (gp120)

Human immunodeficiency virus 1 (HIV-1) surface glycoprotein gp120 is the exterior subunit of the viral envelope complex (Env), serving as the primary mediator of viral attachment to host cells [3, 4]. It is generated from the proteolytic cleavage of the gp160 precursor and exists as a trimeric spike on the virion surface, non-covalently associated with the transmembrane subunit gp41 [3, 6]. The core biological function of gp120 is to bind with high affinity to the CD4 receptor on helper T-cells and macrophages, which induces conformational changes that expose co-receptor binding sites for CCR5 or CXCR4 [1, 9, 11]. These interactions trigger the fusion machinery of gp41, allowing the viral capsid to enter the host cytoplasm [4, 6]. Despite being a major target for neutralizing antibodies, gp120 utilizes a dense 'glycan shield' of N-linked sugars and high sequence variability to evade the host immune response [3, 8, 13]. Therapeutic agents like fostemsavir, a licensed attachment inhibitor, target gp120 by binding to its conserved CD4-binding pocket and preventing initial cell attachment [1, 10, 14]. However, the protein's extreme mutability remains a significant hurdle for drug resistance and the development of a preventative vaccine [3, 13].

Other names

Envelope glycoprotein gp120Surface glycoproteinSUHIV-1 gp120gp160 subunit

Attachment inhibition through direct binding to the gp120 protein, which prevents the initial interaction between the HIV-1 virus and the host CD4 receptor, thereby blocking viral entry.