Human immunodeficiency virus type 1 glycoprotein 41 prehairpin fusion intermediate (HIV-1 gp41 PHI)

The Human immunodeficiency virus type 1 (HIV-1) glycoprotein 41 (gp41) prehairpin fusion intermediate is a transient, extended conformational state of the viral transmembrane protein that occurs during the process of viral entry (Chan & Kim, 1998, Cell). Following the binding of the gp120 subunit to host cell receptors, gp41 undergoes a structural rearrangement that inserts its hydrophobic fusion peptide into the target cell membrane, bridging the virus and the host cell (UniProt, P04578). In this intermediate state, the N-terminal heptad repeat (NHR) regions form a triple-stranded coiled-coil that is temporarily exposed before collapsing into a stable six-helix bundle (6HB) with the C-terminal heptad repeats (CHR) (Eggink et al., 2010, JBC). This transition provides the energy necessary for membrane fusion and subsequent viral core entry. Therapeutic agents known as fusion inhibitors, such as Enfuvirtide, specifically target this intermediate by binding to the exposed NHR coiled-coil, thereby preventing the formation of the 6HB and blocking infection (Wild et al., 1994, PNAS; FDA, 2003).

Other names

gp41 pre-hairpin intermediatePre-hairpin fusion intermediatePHIHIV-1 gp41 fusion intermediategp41 NHR-exposed intermediate

Fusion inhibition by binding to the N-terminal heptad repeat (NHR) region of the gp41 prehairpin intermediate, which prevents the subsequent interaction with the C-terminal heptad repeat (CHR) and the formation of the six-helix bundle (6HB) required for membrane fusion (Chan & Kim, 1998, Cell; FDA, 2003).