Human immunodeficiency virus 1 envelope glycoprotein 120 CD4-binding site (HIV-1 gp120 CD4bs)

The HIV-1 envelope glycoprotein 120 (gp120) CD4-binding site (CD4bs) is a highly conserved region of the viral spike responsible for initiating infection by binding to the host CD4 receptor (Kwong, P. D., et al. Nature, 1998). Because of its critical role in viral entry, the CD4bs is a primary target for broadly neutralizing antibodies (bNAbs) such as VRC01 (Zhou, T., et al. Science, 2010). The eOD-GT8 (engineered Outer Domain-Germline Targeting 8) is a synthetic immunogen designed to mimic the CD4bs in a way that specifically activates germline B cells capable of evolving into VRC01-class antibodies (Jardine, M. D., et al. Science, 2013). This target is central to germline-targeting vaccine strategies, which aim to guide the immune system through a specific maturation pathway to achieve broad protection against diverse HIV-1 strains (Leggat, D. J., et al. Science, 2022). In its native state on the HIV-1 Env trimer, the CD4bs is partially shielded by glycans and conformational masking, making it a challenging but essential focus for therapeutic and prophylactic interventions.

Other names

CD4-binding siteCD4bseOD-GT8HIV-1 Env gp120 CD4-binding siteEngineered Outer Domain-Germline Targeting 8HIV-1 Env gp120 CD4-binding site as mimicked on eOD-GT8 immunogen and native Env

The primary mechanism involves the competitive inhibition of the interaction between the viral gp120 protein and the host CD4 receptor, thereby preventing viral attachment and subsequent entry into target cells (Zhou, T., et al. Science, 2010).