HIV-1 subtype C envelope glycoprotein gp140 trimer (gp140)

The HIV-1 subtype C envelope glycoprotein gp140 trimer is a soluble, recombinant protein complex that mimics the native trimeric envelope (Env) spike of the Human Immunodeficiency Virus type 1 (PNAS, 2012) [1]. Subtype C is the most widespread clade of HIV-1, accounting for approximately half of all global infections, particularly in sub-Saharan Africa and India (PMC, 2022) [5]. The gp140 trimer consists of the gp120 surface subunit and the ectodomain of the gp41 transmembrane subunit, which together mediate the virus's ability to attach to and enter host CD4+ T-cells (PMC, 2015; MyBioSource) [3, 6]. As a primary target for the humoral immune response, this trimer is a central focus for vaccine development aimed at eliciting broadly neutralizing antibodies (bNAbs) that can block viral entry across diverse strains (PNAS, 2012; PMC, 2017) [1, 10]. Therapeutic strategies targeting this molecule include attachment inhibitors like fostemsavir, which binds to gp120, and passive immunization with monoclonal bNAbs such as VRC01 and PGT121 (Lancet HIV, 2015; PMC, 2019) [12, 13]. Challenges in targeting the gp140 trimer include the virus's high mutation rate, extensive glycosylation (the 'glycan shield'), and the presence of immunodominant non-neutralizing epitopes that can divert the immune response (PMC, 2022; PMC, 2017) [5, 10].

Other names

HIV-1 Envgp140 SOSIPSoluble HIV-1 envelope glycoproteinHIV-1 subtype C EnvHIV-1 envelope spike(gp120/gp41)3

Drugs and antibodies targeting the gp140 trimer primarily act by inhibiting viral entry into host cells. Broadly neutralizing antibodies (bNAbs) bind to conserved epitopes on the trimer surface, such as the CD4 binding site or the V1V2 apex, to sterically block receptor engagement or prevent the conformational changes required for membrane fusion (PNAS, 2012; PMC, 2017) [1, 10]. Small molecule attachment inhibitors, such as fostemsavir, bind directly to the gp120 subunit to lock it in a conformation that is incompetent for CD4 binding, thereby preventing the initial step of the infection cycle (Lancet HIV, 2015) [12].