HIV-1 envelope glycoprotein gp41 (gp41) (gp41)

The HIV-1 envelope glycoprotein gp41 (gp41) is a transmembrane subunit of the viral envelope protein (Env) that is essential for HIV-1 entry into host cells [1.1.2, 1.2.2]. The gp41-derived P1 peptide is a conserved 35-amino acid sequence (residues 650–685) located within the Membrane Proximal External Region (MPER) of the protein [1.1.1, 1.1.3]. This specific region plays a critical role in mediating the fusion of viral and cellular membranes and is also involved in the mucosal transcytosis of the virus by binding to galactosylceramide (GalCer) receptors on epithelial cells [1.1.1, 1.2.1]. Because the MPER is highly conserved across different HIV-1 clades and contains epitopes for broadly neutralizing antibodies such as 2F5 and 4E10, it is a primary target for both fusion-inhibiting drugs and prophylactic vaccine development [1.1.3, 1.3.2]. Therapeutic strategies targeting this region include the fusion inhibitor enfuvirtide and vaccine candidates like MYM-V101, which utilize the P1 peptide as an immunogen to elicit protective mucosal and systemic antibodies [1.1.2, 1.3.5]. Additionally, the P1 peptide has been shown to possess adjuvant-like properties, inducing the expression of thymic stromal lymphopoietin (TSLP) to modulate the immune response [1.2.1].

Other names

gp41Transmembrane glycoprotein gp41Membrane proximal external region (MPER)P1 peptideEnv gp41

Fusion inhibition by preventing the formation of the six-helix bundle (6HB) required for membrane merger; neutralization of viral infectivity through antibody binding to the MPER; and blockade of mucosal transcytosis by interfering with GalCer binding.