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

The Human immunodeficiency virus type 1 (HIV-1) glycoprotein 41 (gp41) membrane-proximal external region (MPER) is a highly conserved, tryptophan-rich sequence located at the C-terminus of the gp41 ectodomain, adjacent to the viral transmembrane anchor (Sheng et al., 2014). It plays a pivotal role in the viral entry process by facilitating the fusion of the viral envelope with the host cell plasma membrane (Cardoso et al., 2005). Due to its critical function and low sequence variability across diverse HIV-1 clades, the MPER is a major target for broadly neutralizing antibodies (bNAbs) such as 4E10, 2F5, and 10E8 (Huang et al., 2012). These antibodies, particularly 4E10, recognize a linear epitope within the MPER and block the transition of gp41 into its fusogenic six-helix bundle conformation, thereby preventing infection (Sun et al., 2008). However, the MPER is partially occluded by the viral membrane and is only transiently exposed during the fusion process, making it a difficult target for vaccine-induced immunity (Haynes et al., 2005). Furthermore, some MPER-directed antibodies exhibit polyreactivity with host phospholipids, which poses potential safety concerns regarding autoimmunity and complicates the development of MPER-based therapeutics (Alam et al., 2009).

Other names

gp41 MPERMembrane-proximal external region of gp41HIV-1 envelope glycoprotein gp41 MPER4E10 epitope

Neutralization of viral entry by binding to the MPER and inhibiting the conformational changes of gp41 required for fusion of the viral and host cell membranes (Sun et al., 2008).