Lipid composition modulates the interaction of peptides deriving from Herpes Simplex Virus type I glycoproteins B and H with biomembranes

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 favouring the necessary micro- and mesoscopic lipid re-arrangements. As a result of their high propensity to partition into the membrane interface, several membranotropic regions of these glycoproteins are expected to participate in the membrane distortion necessary for fusion. In this work, we perform an EPR study focused on the role played by the membrane composition in tuning the interaction between lipid bilayers and two peptides, gH626–644 and gB632–650, that derive from 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 localises close to the hydrophilic bilayer surface, while gB632-650 penetrates deeply into the membrane. The 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. 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.