Human immunodeficiency virus type 1 envelope glycoprotein gp120 V2 region (HIV-1 gp120 V2)

The HIV-1 gp120 V2 region is a highly variable segment of the envelope glycoprotein (Env) that forms part of the V1/V2 domain at the apex of the viral trimer (McLellan et al., 2011, Nature). It plays a crucial role in the structural integrity of the Env trimer and the regulation of conformational transitions necessary for viral entry into host cells. Beyond its structural role, the V2 region interacts with host cell receptors, including the integrin alpha-4 beta-7, which is thought to facilitate viral homing to gut-associated lymphoid tissues (Cicala et al., 2008, PNAS). This region is a significant target for the host immune response, and antibodies directed against the V2 loop were identified as a key correlate of reduced infection risk in the RV144 HIV vaccine trial (Haynes et al., 2012, N Engl J Med). Therapeutic strategies often focus on this region using broadly neutralizing antibodies (bnAbs) like PG9 and PG16, which recognize conserved glycan-peptide epitopes at the trimer apex (Walker et al., 2009, Science). However, the extreme sequence diversity and the presence of a dense glycan shield present significant challenges for drug and vaccine design. Understanding the V2 region's dynamics is essential for developing interventions that can overcome viral escape mechanisms.

Other names

V2 loopSecond variable loop of gp120V1/V2 domaingp120 V2

Neutralization of viral entry by blocking interaction with host receptors and mediating antibody-dependent cellular cytotoxicity (ADCC) (Haynes et al., 2012, N Engl J Med; Walker et al., 2009, Science).