Human immunodeficiency virus 1 envelope glycoprotein gp120 variable loop 2 (HIV-1 gp120 V2 loop)

The HIV-1 envelope glycoprotein gp120 variable loop 2 (V2 loop) is a critical structural domain located at the apex of the HIV-1 envelope (Env) trimer, which serves as the primary machinery for viral entry into host cells. Biologically, the V2 loop plays a dual role: it is essential for the stabilization of the prefusion Env trimer and it facilitates viral dissemination by interacting with host cell receptors, most notably the alpha-4-beta-7 (α4β7) integrin. Because it is one of the few exposed regions on the native Env spike, it is a primary target for the host's humoral immune response and a focal point for HIV-1 vaccine design. In the context of therapeutics, the V2 loop is the target of several broadly neutralizing antibodies (bNAbs), such as PG9 and PG16, which recognize quaternary epitopes involving the V2 region and associated glycans. Notably, the RV144 clinical trial provided evidence that antibodies directed against the V2 loop were a primary correlate of reduced infection risk, highlighting its potential as a protective immunogen. However, the target presents significant challenges for drug development due to its extreme sequence diversity and heavy glycosylation, which allow the virus to rapidly evolve escape mutants and evade immune detection.

Other names

Second variable loop of gp120V2 region of gp120Env V2 loopV1/V2 apexV1V2 domain

Broadly neutralizing antibodies (bNAbs) target the V2 loop to block viral entry by preventing binding to the CD4 receptor or co-receptors (CCR5/CXCR4) and by stabilizing the envelope trimer in a non-functional state. Non-neutralizing antibodies may also trigger antibody-dependent cellular cytotoxicity (ADCC) by binding to the V2 region on the surface of infected cells.