Human immunodeficiency virus type 1 envelope glycoprotein 41 membrane-proximal external region (HIV-1 gp41 MPER) (HIV-1 gp41 MPER)

The HIV-1 envelope glycoprotein 41 (gp41) is a transmembrane protein that mediates the fusion of the viral envelope with the host cell membrane (UniProt P04578). The Membrane-Proximal External Region (MPER) is a highly conserved, tryptophan-rich segment of gp41 located adjacent to the transmembrane domain (PubMed: 22110160). This region is a major target for broadly neutralizing antibodies (bNAbs) such as 4E10, 2F5, and 10E8, which are capable of neutralizing a diverse array of HIV-1 strains (PubMed: 23154938). The 4E10 epitope specifically represents a linear sequence within the C-terminal portion of the MPER that is essential for the fusion process (PubMed: 15694430). Therapeutic strategies targeting the MPER aim to block the formation of the six-helix bundle or the pre-hairpin intermediate, effectively preventing viral entry (PubMed: 21835245). Despite its conservation, the MPER is poorly immunogenic and some antibodies targeting it exhibit lipid reactivity, posing challenges for vaccine development (PubMed: 17604450).

Other names

gp41 MPERMembrane-proximal external region4E10 epitope10E8 epitope2F5 epitopeHIV-1 gp41

Inhibition of viral-host membrane fusion by binding to the MPER and blocking the transition of gp41 into its post-fusion six-helix bundle conformation, thereby preventing the formation of the fusion pore (PubMed: 21835245).