Dedicated experimental systems used for the study of HSV1 entry. (a) Reducing biological complexity from the most native system, virus entry into intact host cells [24], to gradually less complex subsystems, that is, virus entry into synaptosomes [24] or liposomes, and study of glycoproteins on the viral surface. (b) HSV1 glycoprotein B (gB), a key component of the fusion machinery, bound to liposomes used as display platform for direct visualization of fusion protein interaction with its target membrane. Sub-volume averaging was used to reconstruct the gB–lipid bilayer complex (middle panel, light grey) [42]. The EM reconstruction together with fitting of the gB crystal structure revealed the mode of interaction to the membrane. Lateral interaction of gB induced protein coat or belt formation on liposomes. Placing back the EM reconstruction in the experimentally determined orientations (right panel) allowed analysing the lateral interactions [42].