Human Immunodeficiency Virus Type 1 Envelope Glycoprotein gp120 (gp120)

The HIV-1 envelope glycoprotein gp120 is a heavily glycosylated protein exposed on the surface of the human immunodeficiency virus (HIV) envelope. It plays a central role in viral entry into host cells by mediating attachment to specific cell surface receptors, primarily CD4 and chemokine co-receptors such as CCR5 or CXCR4. Gp120 first binds to CD4 receptors on target cells—primarily helper T-cells—via electrostatic interactions as well as van der Waals forces and hydrogen bonds. This binding induces conformational changes in both gp120 and associated gp41 that are essential for subsequent steps in viral entry. After CD4 engagement, further conformational changes expose or create binding sites for chemokine co-receptors (CCR5 or CXCR4), facilitating membrane fusion between virus and host cell. Gp120's extensive glycosylation shields conserved protein surfaces from immune recognition. Its variable regions (notably V1-V2 loops) contribute to antigenic diversity while modulating receptor usage; V3 loop sequence determines co-receptor specificity (CCR5 vs. CXCR4). It remains under investigation as a potential site of vulnerability for vaccines or inhibitors aiming at blocking receptor/co-receptor interactions or inducing broadly neutralizing antibodies against conserved epitopes within this protein.

Blocks viral entry by interfering with gp120 interaction with CD4 or chemokine co-receptors (CCR5/CXCR4)