title: Lipid composition modulates the interaction of peptides deriving from herpes simplex virus type I glycoproteins B and H with biomembranes.
abstract: Lipid membranes play a key role in the viral life cycle. Enveloped viruses particularly require a sequence of fusion and fission events between the viral envelope and the target membranes for entry into the cell and egress from it. These processes are controlled by one or more viral glycoproteins that undergo conformational changes favoring the necessary micro- and mesoscopic lipid re-arrangements. Multiple regions from these glycoproteins are thought to interact with the membranes, according to a concerted mechanism, in order to generate the distortion necessary for fusion. In this work, we perform an EPR study on the role played by the membrane composition in tuning the interaction between lipid bilayers and two peptides, gH626-644 and gB632-650, that are highly fusogenic fragments of the gH and gB glycoproteins of herpes simplex virus. Our results show that both peptides interact with lipid bilayers, perturbing the local lipid packing. gH626-644 localizes close to the hydrophilic bilayer surface, while gB632-650 penetrates deeply into the membrane. Chain perturbation by the peptides increases in the presence of charged phospholipids. Finally, cholesterol does not alter the ability of gB632-650 to penetrate deeply in the membrane, whereas it limits penetration of the gH626-644 peptide to the more external layer. The different modes of interaction result in a higher fusogenic ability of gB632-650 towards cholesterol-enriched membranes, as demonstrated by lipid mixing assays. These results suggest that the mechanism of action of the gH and gB glycoproteins is modulated by the properties and composition of the phospholipid bilayer.
authors.affiliation: Department of Chemistry, University of Naples, Monte Sant'Angelo, Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Vitiello
authors.forename: Annarita
authors.initials: A
authors.lastname: Falanga
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Galdiero
authors.forename: Derek
authors.initials: D
authors.lastname: Marsh
authors.forename: Stefania
authors.initials: S
authors.lastname: Galdiero
authors.forename: Gerardino
authors.initials: G
authors.lastname: D'Errico
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D004578:Electron Spin Resonance Spectroscopy; D008051:Lipid Bilayers / Q000737:chemistry*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D017433:Protein Structure, Secondary; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D008051:Lipid Bilayers; D010455:Peptides; D010743:Phospholipids; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus; C044200:glycoprotein H, herpes simplex virus type 1