Abstract

The fusogenic function of HIV-1 gp41 transmembrane Env subunit relies on two different kinds of structural elements: i) a collapsible ectodomain structure (the hairpin or six-helix bundle) that opens and closes, and ii) two membrane- transferring regions (MTRs), the fusion peptide (FP) and the membrane-proximal external region (MPER), which ensure coupling of hairpin closure to apposition and fusion of cell and viral membranes. The isolation of naturally produced short peptides and neutralizing IgG-s, that interact with FP and MPER, respectively, and block viral infection, suggests that these conserved regions might represent useful targets for clinical intervention. Furthermore, MTR-derived peptides have been shown to be membrane-active. Here, it is discussed the potential use of these molecules and how the analysis of their membrane activity in vitro could contribute to the development of HIV fusion inhibitors and effective immunogens.

Keywords: HIV-1 fusion inhibition, HIV-1 gp41, HIV-1 fusion peptide, HIV-1 MPER, anti-MPER antibody, fusogenic function, collapsible ectodomain structure, fusion peptide, membrane-proximal external region (MPER), fusion of cell and viral membranes, isolation of naturally produced short peptides and neutralizing IgG-s, immunogens