Abstract
This paper discusses physical and structural aspects of the mechanisms herpes simplex virus (HSV) uses for membrane fusion. Calculations show that herpes simplex virus glycoprotein D has such avidity for its receptors that it can hold the virion against the plasma membrane of a neuron strongly enough for glycoprotein B (gB) to disrupt both leaflets of the bilayer. The strong electric field generated by the cell potential across perforations at this disruption would break the hydrogen bonds securing the gB fusion loops, leading to fusion of the plasma and viral membranes. This mechanism agrees with the high stability of the tall trimeric spike structure of gB and is consistent with the probable existence of a more compact initial conformation that would allow it to closely approach the plasma membrane. The release of the fusion domains by disruption of hydrogen bonds is shared with the endocytotic entry pathway where, for some cell types not punctured by gB, the virus is able to induce inward forces that cause endocytosis and the fusion loops are released by acidification. The puncture-fusion mechanism requires low critical strain or high tissue strain, matching primary tropism of neural processes at the vermillion border. In support of this mechanism, this paper proposes a functional superstructure of the antigens essential to entry and reviews its consistency with experimental evidence.