HIV-1 envelope glycoprotein gp120 V3 loop (HIV-1 gp120 V3-loop)

The HIV-1 envelope glycoprotein gp120 V3 loop is a 35-residue highly variable loop forming the third hypervariable (V3) region on the gp120 outer domain, functioning as the primary determinant of HIV-1 coreceptor specificity—governing whether a viral strain uses CCR5 or CXCR4 for cell entry[2][4]. The V3 loop contains conserved structural elements (an arch, a band, a hydrophobic core, and the backbone)[2], and presents critical epitopes targeted by broadly neutralizing antibodies. The loop is exposed at the apex of gp120 and undergoes conformational changes in response to receptor (CD4) binding, facilitating viral entry and serving as a target for entry inhibitors and neutralizing antibodies. Due to its antigenicity and role in tropism, V3 loop sequence analysis is used in genotypic tropism testing to guide usage of CCR5 antagonists like Maraviroc[4]. Its high variability aids viral immune evasion, posing challenges for vaccine and drug development[2][3].

Other names

gp120 V3 loopThird variable loop of HIV-1 gp120V3 loop of HIV-1 envelope protein

Inhibition of gp120 binding to CCR5 or CXCR4 via blocking the V3 loop's interaction, thus preventing viral entry[2][4]. Neutralization by antibodies targeting conserved V3 epitopes which block coreceptor binding[2].