HIV-1 envelope glycoprotein gp41 membrane-proximal external region (MPER)

The HIV-1 envelope glycoprotein gp41 membrane-proximal external region (MPER) is a highly conserved, tryptophan-rich segment of the gp41 ectodomain located adjacent to the viral transmembrane domain (UniProt P04578). It is essential for the viral-cell membrane fusion process, specifically mediating the transition to the post-fusion state (PubMed: 23021216). Due to its high conservation across various HIV-1 clades, MPER is a major target for broadly neutralizing antibodies (bNAbs) such as 10E8, 2F5, and 4E10, which can neutralize a wide range of viral isolates (NIH: PMC3491132). These antibodies typically recognize MPER in the context of the viral lipid bilayer, which presents a challenge for vaccine design as the region is often sterically shielded or only transiently exposed during fusion (PubMed: 27058958). Despite these challenges, MPER remains a high-priority target for HIV-1 prevention and therapy because of its vulnerability to potent neutralization (PubMed: 30104377). Research continues to focus on creating immunogens that can elicit MPER-specific antibodies without inducing autoreactivity to host lipids (PubMed: 25161314).

Other names

gp41 MPERMembrane-proximal external regionHIV-1 gp41 MPERgp41-MPER

Binding to the MPER prevents the conformational changes in gp41 required for the fusion of the viral envelope with the host cell membrane, thereby neutralizing the virus (PubMed: 23021216).