Human immunodeficiency virus type 1 envelope glycoprotein trimer, V2 apex region (HIV-1 Env V2 apex)

The HIV-1 envelope glycoprotein (Env) trimer is the sole viral protein exposed on the surface of the HIV-1 virion, making it the primary target for neutralizing antibodies. The V2 apex region is a quaternary epitope located at the top of the Env trimer, formed by the association of the V1/V2 loops from three gp120 subunits (Sanders, R. W., & Moore, J. P. (2017). Nature Reviews Immunology, 17(10), 623-636). This region is a major site of vulnerability for broadly neutralizing antibodies (bNAbs) such as PG9, PG16, and PGT145, which recognize a combination of conserved protein residues and N-linked glycans (Walker, L. M., et al. (2009). Science, 326(5950), 285-289). Biologically, the V2 apex is involved in maintaining the trimer in a closed pre-fusion state, and its engagement by bNAbs prevents the conformational transitions required for viral entry into CD4+ T cells (Julien, J. P., et al. (2013). Science, 342(6165), 1477-1483). In the context of infection, the V2 apex is highly variable and heavily glycosylated, which allows the virus to escape most antibody responses; however, the discovery of bNAbs targeting this region has spurred significant interest in structure-based vaccine design and passive immunotherapy (Bonsignori, M., et al. (2011). Journal of Virology, 85(23), 12663-12674). Therapeutic challenges include the rapid evolution of the virus leading to mutational escape and the heterogeneity of the glycan shield across different HIV-1 clades.

Other names

V1/V2 loopV2 apex epitopeHIV-1 Env trimer apexgp120 V1/V2 domain

Broadly neutralizing antibodies bind to the V2 apex, stabilizing the pre-fusion closed conformation of the Env trimer and sterically hindering interaction with host cell receptors, thereby preventing viral entry.