gp120
Summary
gp120 is the HIV envelope surface glycoprotein that binds CD4 and then a chemokine coreceptor, CCR5 or CXCR4, to initiate entry. Its extreme variability and glycan shielding are central obstacles to an effective HIV vaccine.
Detail
The HIV env gene product gp160 is cleaved by a host protease into gp120, which projects from the virion surface, and gp41, which anchors it and mediates membrane fusion. gp120 first engages CD4, undergoing a conformational change that exposes the coreceptor binding site; macrophage-tropic R5 strains use CCR5 and predominate in early infection, while T-cell-tropic X4 strains use CXCR4 and emerge later, correlating with faster CD4 decline. Maraviroc is a CCR5 antagonist exploiting this step, and enfuvirtide blocks gp41-mediated fusion. gp120 has five hypervariable loops and is heavily glycosylated, so neutralizing antibodies are largely strain-specific and the conserved CD4 binding site is sterically shielded; broadly neutralizing antibodies against it are rare and slow to develop. Homozygous CCR5-delta32, present in roughly one per cent of people of northern European descent, prevents R5 entry and confers near-complete resistance to infection.
Sources
- Levinson Medical Microbiology and Immunology
- Janeway's Immunobiology
Reviewed by AnkiBoss editorial — medical student review. Information here is for study reference only and is not medical advice. Spotted an error? Let us know.