Human immunodeficiency virus type 1 envelope glycoprotein gp120–gp41 interface (HIV-1 Env interface)

The Human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) is a heterotrimeric complex composed of three gp120 surface subunits and three gp41 transmembrane subunits [UniProt P04578]. The gp120–gp41 interface region is a critical structural domain where these subunits non-covalently associate to maintain the Env trimer in a metastable, pre-fusion conformation [Blattner et al., 2014]. This interface is a primary target for several classes of broadly neutralizing antibodies (bNAbs), such as PGT151 and 35O22, which recognize epitopes spanning both subunits [Huang et al., 2014]. By binding to this region, these agents stabilize the trimer and prevent the dramatic conformational changes—specifically the shedding of gp120 and the extension of the gp41 fusion peptide—required for membrane fusion [Kong et al., 2016]. Because the interface is essential for viral viability, it remains relatively conserved, making it an attractive target for long-acting biologics and vaccine immunogen design [Lee et al., 2016]. Therapeutic intervention at this site aims to provide broad protection against diverse HIV-1 strains by blocking the earliest stages of the viral life cycle. This approach is particularly relevant for preventing viral entry and reducing the latent reservoir in infected individuals.

Other names

gp120-gp41 junctionHIV-1 Env trimer interfacegp120/gp41 interface

Stabilization of the pre-fusion Env trimer and inhibition of the conformational rearrangements required for viral-host membrane fusion [Blattner et al., 2014; Huang et al., 2014].