title: Membrane-transferring regions of gp41 as targets for HIV-1 fusion inhibition and viral neutralization.
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.
authors: Unidad de Biofísica (CSIC-UPV/EHU) and Dpt. de Bioquímica y Biología Molecular, Universidad del País Vasco, Aptdo. 644, E-48080 Bilbao, Spain.
authors: Nerea
authors: N
authors: Huarte
authors: Maier
authors: M
authors: Lorizate
authors: Enrique
authors: E
authors: Pérez-Payá
authors: José L
authors: JL
authors: Nieva
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D015483:HIV Antibodies / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D023581:HIV Fusion Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D010455:Peptides / Q000494:pharmacology*; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010455:Peptides