Human immunodeficiency virus type 1 envelope glycoprotein gp120 (HIV-1 gp120) – monoclonal antibody 17b (mAb 17b) interaction (HIV-1 gp120–17b)

The HIV-1 gp120 – mAb 17b interaction represents a critical structural state in the entry process of the Human Immunodeficiency Virus type 1. HIV-1 gp120 is the exterior envelope glycoprotein that facilitates viral entry by binding to the host cell receptor CD4 and subsequently to a co-receptor, either CCR5 or CXCR4 (Kwong et al., 1998). The monoclonal antibody 17b (mAb 17b) is a human antibody that specifically recognizes a CD4-induced (CD4i) epitope on gp120, which is part of the conserved co-receptor binding site (Thali et al., 1993). This epitope is hidden in the native, unliganded state of the envelope trimer and only becomes exposed after the conformational change triggered by CD4 binding. Because the 17b binding site is essential for viral-cell fusion and is highly conserved across different HIV-1 strains, it is a primary target for the development of entry inhibitors and neutralizing antibodies. However, the transient and sterically restricted nature of this epitope on the viral surface poses a significant challenge for therapeutic intervention. Modern strategies often utilize CD4-mimetic compounds to stabilize the gp120-17b-like conformation, thereby enhancing the susceptibility of the virus to neutralization (UniProtKB P04578).

Other names

CD4-induced epitopeCD4i epitopegp120 co-receptor binding sitegp120-17b complexBridging sheet epitope

The interaction involves the binding of mAb 17b to the CD4-induced (CD4i) epitope on the gp120 subunit of the HIV-1 envelope glycoprotein. This epitope is formed by the rearrangement of the V1/V2 and V3 loops and the formation of a four-stranded beta-sheet known as the bridging sheet (Kwong et al., 1998). By binding to this site, mAb 17b sterically hinders the interaction between gp120 and the host co-receptors CCR5 or CXCR4, which is a prerequisite for the subsequent insertion of the gp41 fusion peptide into the host cell membrane and successful viral entry (Thali et al., 1993).