Human immunodeficiency virus envelope glycoprotein gp120 (gp120)

Human immunodeficiency virus envelope glycoprotein gp120 is a heavily glycosylated surface protein of HIV-1 and HIV-2 that mediates virus entry into host cells[1][5][6]. It is produced as part of a precursor (gp160), which is cleaved to yield gp120 (surface subunit) and gp41 (transmembrane subunit); these form trimeric complexes on the viral envelope that serve as the viral "spike"[5][1]. Gp120 is responsible for initial binding to the host CD4 receptor, primarily on T-helper lymphocytes, and undergoes conformational changes that allow subsequent binding to a coreceptor (usually CCR5 or CXCR4), which triggers fusion via gp41[1][3][6]. The structure of gp120 is notable for its complex fold with inner and outer domains, extensive variable and glycosylated loops (notably V1–V5), and a highly conformational, discontinuous CD4-binding site[5][6][4][2]. Its antigenic surface is shielded from immune detection both by variable loops and a dense glycan layer, conferring formidable immune evasion capabilities[6][4]. Gp120 is the primary target for neutralizing antibodies in natural infection, and hence for HIV vaccine and therapies; however, its high sequence variability and structural plasticity make broad neutralization challenging[6][4][2]. Gp120 is an established and central drug target: entry inhibitors and neutralizing antibodies block gp120 interactions or induce its non-fusogenic conformations, preventing virus-cell fusion and infection. Therapies either block gp120 binding to CD4 or coreceptors, or exploit structural vulnerabilities with potent antibodies or engineered molecules[6][4][1].

Other names

HIV envelope glycoproteinEnvelope glycoprotein GP120EnvHIV-1 gp120Surface glycoprotein (SU)HIV envelope glycoprotein gp160 (gp160 is the precursor, not itself a therapeutic target, but often grouped in literature)

Blockade of CD4 binding Blockade of chemokine coreceptor (CCR5/CXCR4) binding Neutralization of structural elements (V3 loop, CD4-binding site) Allosteric inhibition (conformational locking by antibodies or small molecules)