title: Interaction between dengue virus fusion peptide and lipid bilayers depends on peptide clustering.
abstract: Dengue fever is one of the most widespread tropical diseases in the world. The disease is caused by a virus member of the Flaviviridae family, a group of enveloped positive sense single-stranded RNA viruses. Dengue virus infection is mediated by virus glycoprotein E, which binds to the cell surface. After uptake by endocytosis, this protein induces the fusion between viral envelope and endosomal membrane at the acidic environment of the endosomal compartment. In this work, we evaluated by steady-state and time-resolved fluorescence spectroscopy the interaction between the peptide believed to be the dengue virus fusion peptide and large unilamellar vesicles, studying the extent of partition, fusion capacity and depth of insertion in membranes. The roles of the bilayer composition (neutral and anionic phospholipids), ionic strength and pH of the medium were also studied. Our results indicate that dengue virus fusion peptide has a high affinity to vesicles composed of anionic lipids and that the interaction is mainly electrostatic. Both partition coefficient and fusion index are enhanced by negatively charged phospholipids. The location determined by differential fluorescence quenching using lipophilic probes demonstrated that the peptide is in an intermediate depth in the hemilayers, in-between the bilayer core and its surface. Ultimately, these data provide novel insights on the interaction between dengue virus fusion peptide and its target membranes, namely, the role of oligomerization and specific types of membranes.
authors.affiliation: Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Fausto
authors.initials: F
authors.lastname: Stauffer
authors.forename: Manuel Nuno
authors.initials: MN
authors.lastname: Melo
authors.forename: Fabiana A
authors.initials: FA
authors.lastname: Carneiro
authors.forename: Francisco J R
authors.initials: FJ
authors.lastname: Sousa
authors.forename: Maria A
authors.initials: MA
authors.lastname: Juliano
authors.forename: Luiz
authors.initials: L
authors.lastname: Juliano
authors.forename: Ronaldo
authors.initials: R
authors.lastname: Mohana-Borges
authors.forename: Andrea T
authors.initials: AT
authors.lastname: Da Poian
authors.forename: Miguel A R B
authors.initials: MA
authors.lastname: Castanho
mesh_terms: D000595:Amino Acid Sequence; D003716:Dengue Virus / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008051:Lipid Bilayers / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D009994:Osmolar Concentration; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D053835:Unilamellar Liposomes / Q000378:metabolism; D014760:Viral Fusion Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D008051:Lipid Bilayers; D010455:Peptides; D053835:Unilamellar Liposomes; D014760:Viral Fusion Proteins