HIV-1 envelope glycoprotein 41 membrane-proximal external region (MPER) - LELDKWASL epitope (HIV-1 gp41 MPER (LELDKWASL))

The HIV-1 gp41 membrane-proximal external region (MPER) is a highly conserved, tryptophan-rich segment of the HIV-1 envelope glycoprotein (gp41) located just outside the viral membrane (Montero et al., 2008, Microbiology and Molecular Biology Reviews). The LELDKWASL sequence is a specific linear epitope within the MPER that is recognized by the broadly neutralizing antibody (bNAb) 2F5 (Muster et al., 1993, Journal of Virology). Biologically, this region is essential for the fusion of the viral envelope with the host cell membrane, a process triggered after gp120 binds to CD4 and coreceptors (Zwick et al., 2001, Journal of Virology). In the context of disease, the MPER is a critical target for HIV-1 prevention and treatment because its conservation suggests it is functionally indispensable for the virus (Haynes et al., 2005, Science). Therapeutic strategies involving this target include the administration of monoclonal antibodies like 2F5 or the design of vaccines intended to elicit similar MPER-specific antibodies. However, the epitope's proximity to the lipid bilayer and its tendency to elicit autoreactive antibodies that bind to host lipids like cardiolipin pose significant hurdles for clinical application (Haynes et al., 2005, Science; Alam et al., 2009, PNAS).

Other names

2F5 epitopegp41 MPERHIV-1 gp41 MPERLELDKWASL peptideMembrane-proximal external region of gp41

Inhibition of viral-cell membrane fusion by sterically blocking the conformational transition of gp41 into its pre-hairpin intermediate state, thereby preventing the formation of the six-helix bundle required for fusion (Zwick et al., 2001, Journal of Virology).