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 single RNA virus. Dengue virus infection is mediated by virus glycoprotein E, which binds to the cell surface and induces the fusion between viral envelope and endosomal membrane at the acidic environment of the endosomal compartment. In this work, we evaluated by means of physical-chemistry methodologies the interaction between the peptide believed to be the dengue virus fusion peptide and large unilamellar vesicles, studying the extent of partition, fusion capacity, location and orientation in membrane. The role of the bilayer composition (neutral and anionic phospholipids), ionic strength and pH of the medium, and reducing agents were also studied. Our results indicate that Dengue virus fusion peptide has a high affinity to vesicles composed by anionic lipids and that the interaction is mainly electrostatic. Both partition coefficient and fusion index are enhanced by negative charged phospholipids. The location determined by differential fluorescence quenching using lipophilic probes demonstrated that the peptide is in an intermediate depth in the bilayers, in-between the bilayer core and its surface. The orientational probability density function of the Trp residue calculated by fluorescence linear dichroism data showed that the range of allowed orientations is moderate, ranging from @40° to @70°. Ultimately, these data provides novel insights on the mechanism of dengue virus fusion peptide and specific types of membranes.
Supported by: CAPES/GRICES, FAPERJ and CNPq.