Fig. 6.

Schematic model for the fusion mechanism based on the identified intermediates. (A) The bulky glycoprotein spikes in close proximity to gD, which are not involved in cell entry, act as spacers. Thus, gD cannot bind to its specific receptor, and the fusion process is not initiated. (B) Fusion can only be initiated if the contact of the entry-associated glycoprotein gD with its cellular receptor is not sterically hindered. (C) Binding of gD to its receptor might be paralleled or preceded by nonessential interactions of gB with heparan sulfate proteoglycans. (D) After receptor binding, gD undergoes a conformational change and interacts with gH/gL. This induces gH/gL to also change conformation and to flip out one segment that binds to the plasma membrane. This connects the two membranes, brings them close together and enables lipid mixing (E). Glycoprotein B is recruited to the gD/gH/gL complex by the conformational switch of gH/gL and binds to the plasma membrane (F). The fusion pore forms stabilized by gB.