HIV-1 envelope glycoprotein membrane fusion (mediated by gp41) (HIV-1 Env-mediated fusion; sometimes "gp41-mediated fusion")

The process of HIV fusion is catalyzed by the viral envelope protein complex, primarily the gp41 subunit, which mediates the merger of viral and cellular membranes[2][3][4][7]. Fusion initiation requires the sequential binding of envelope protein gp120 to the cellular receptor CD4 and a coreceptor (CCR5 or CXCR4), which triggers conformational changes exposing the fusion peptide of gp41[3][4]. The gp41 folds back on itself, forming a stable six-helix bundle (“trimer of hairpins”) that brings the virus and cell membranes into proximity, allowing their merger[2][3]. Therapeutic agents that target HIV fusion (most notably Enfuvirtide) block these conformational rearrangements, precluding viral entry and replication[3]. This mechanistic event is conserved across many enveloped viruses, but the structure and triggering mechanism are specific for HIV and are a focus of drug development and vaccine design[2][4][6]. HIV fusion is a defining step in productive infection and is exploited both in drug discovery and vaccine design by targeting conserved epitopes within gp41 and the fusion peptide[2][4][6]. Structural understanding of the fusion mechanism has propelled high-affinity biologics and antibody therapies designed to neutralize HIV by locking the fusion protein in non-functional conformations[2]. While "HIV fusion" might refer narrowly to the process, in a drug-targeting context it generally refers to the protein complex and its activity, making it a valid target entry. The most specific molecular reference is "gp41-mediated fusion event."[3][2]

Other names

HIV fusionHIV entryHIV-1 Env-mediated fusiongp41-mediated fusionHIV membrane fusion

Blockage of conformational changes in gp41, preventing formation of the six-helix bundle required for membrane fusion. Inhibition of gp120/CD4 interaction to prevent exposure of gp41 fusion peptide.