Human immunodeficiency virus type 1 envelope glycoprotein 140 (HIV-1 gp140)

Human immunodeficiency virus type 1 envelope glycoprotein 140 (HIV-1 gp140) is a soluble, trimeric form of the HIV-1 envelope protein, comprising the gp120 subunit and the ectodomain of the gp41 subunit (UniProt: P04578). It serves as a primary target for the development of vaccines and broadly neutralizing antibodies (bNAbs) because it mediates viral entry into host cells by binding to the CD4 receptor and coreceptors like CCR5 or CXCR4 (NIH: NIAID, 2023). The gp140 protein contains several highly conserved epitopes, including the CD4 binding site (CD4bs), the V1/V2 apex, and the V3-glycan patch, which are critical for viral fitness and are targeted by therapeutic antibodies such as VRC01 and PGT121 (PubMed: 24171578). In clinical research, engineered gp140 trimers, such as the SOSIP design, are used to mimic the native viral spike to elicit protective immune responses (PubMed: 24039251). However, the high mutation rate of HIV-1 and the presence of a dense glycan shield present significant challenges for drug and vaccine design, often leading to viral escape (Nature, 2020).

Other names

gp140HIV-1 EnvHIV-1 envelope proteingp120-gp41 ectodomainHIV-1 Env gp140 epitopes

Neutralization of viral entry by blocking CD4 binding sites or preventing the conformational changes required for membrane fusion (PubMed: 24171578).