HIV-1 envelope glycoprotein gp120 third variable region (V3 loop) (V3 loop)

The HIV-1 envelope glycoprotein V3 loop is a ~34–35 amino acid segment within the gp120 subunit of the envelope spike, forming a prominent, flexible loop essential for virus attachment and entry into target cells. It governs co-receptor specificity (CCR5 or CXCR4), dictates viral tropism, and significantly impacts antibody neutralization. Despite high sequence variability—especially in its crown—the V3 loop maintains a conserved structural core, namely a β-hairpin motif, required for its function. Vaccine and therapeutic strategies frequently target the V3 loop due to its exposure during viral entry and its immunogenic properties, though effective targeting is challenged by both sequence variation and conformational masking within the viral trimer. Neutralizing antibodies and engineered protein inhibitors have shown activity by binding to exposed conformations of V3, blocking virus-cell fusion and entry.

Other names

V3 loopgp120 V3 loopHIV-1 Env V3Third variable region of HIV-1 envelope glycoproteinHIV-1 envelope glycoprotein gp120 V3

Neutralization of virus by binding to and blocking the V3 loop, preventing interaction with chemokine co-receptors; Stabilization of gp120 in nonfunctional conformations (e.g., broadly neutralizing DARPins trap the V3 loop in a helical structure, preventing entry); Antibody-dependent virus neutralization