GP120

gp120 is a surface glycoprotein of the human immunodeficiency virus type 1 (HIV-1). It is part of the envelope glycoprotein gp160, which is produced as a precursor and then cleaved by host proteases into gp120 and gp41. gp120, together with gp41, forms the trimeric envelope spike that decorates the viral surface and mediates entry into host cells.

The primary function of gp120 is to bind to the host cell to initiate infection. It attaches first to the CD4 receptor, mainly on T helper cells and other CD4-expressing cells, via a conserved CD4 binding site. Binding to CD4 induces conformational changes in gp120 that expose or create a binding site for a coreceptor, typically CCR5 or CXCR4. Engagement of a coreceptor triggers further rearrangements that bring gp41 into the correct position to catalyze fusion between the viral envelope and the host cell membrane, allowing viral entry.

gp120 is characterized by extensive glycosylation and a high degree of sequence variability, especially in the outer variable loops V1–V5. This variability, along with the dense glycan shield surrounding a relatively conserved core, helps HIV evade neutralizing antibodies. The CD4 binding site and other regions of gp120 are targets for broadly neutralizing antibodies, but eliciting such responses through vaccination has proven difficult due to antigenic diversity and glycosylation.

Genetically, gp120 is encoded by the env gene of HIV-1. Understanding its structure and interactions remains central to HIV research, including vaccine design and therapeutic interventions targeting viral entry.