Human immunodeficiency virus type 1 glycoprotein 120-CD4 receptor interface (HIV-1 gp120-CD4 interface)

The HIV-1 gp120-CD4 interface is a critical protein-protein interaction site required for the entry of the Human Immunodeficiency Virus type 1 (HIV-1) into host immune cells. The viral envelope glycoprotein gp120, which is the surface subunit of the gp160 precursor, binds to the immunoglobulin-like D1 domain of the host CD4 receptor, primarily expressed on T-helper lymphocytes and macrophages (Kwong et al., 1998, Nature). This high-affinity binding event is the first step of viral entry, inducing a conformational change in the gp120/gp41 trimer that exposes the co-receptor binding site for CCR5 or CXCR4 (NIH, 2023). Therapeutic targeting of this interface includes attachment inhibitors like fostemsavir, which binds to gp120 to prevent CD4 docking, and broadly neutralizing antibodies (bNAbs) such as VRC01 that mimic CD4 binding to neutralize the virus (ViiV Healthcare, 2020; Lynch et al., 2015, Science Translational Medicine). Disrupting this interface is a key strategy in managing multi-drug resistant HIV-1 infections, although the high genetic diversity of the envelope protein remains a significant barrier to universal efficacy (PubMed, 2021). Successful inhibition of this interface prevents the virus from anchoring to the host cell, thereby halting the infection cycle before the fusion of viral and cellular membranes occurs.

Other names

gp120-CD4 binding siteCD4 binding siteCD4bsHIV-1 envelope-CD4 interfacegp120-CD4 interaction site

Attachment inhibition by blocking the interaction between the viral gp120 protein and the host CD4 receptor, thereby preventing viral entry into the cell.