HSV glycoproteins and their roles in virus entry and egress

In the past several years there has been remarkable progress in our understanding of the events leading to herpes simplex virus (HSV) entry into the cells and its egress. Foremost was the realization that HSV entry requires a multigene system; this property differentiates HSV, and herpesviruses in general, from the majority of viruses. The glycoproteins absolutely required for the fusion that leads to HSV entry are gB gD, gH, gL. The receptor binding glycoprotein gD interacts with multiple alternative receptors that belong to unrelated protein families. They are nectin1 and 2, and the herpesvirus entry mediator. In addition, gD encodes a pro-fusion domain, thought to trigger fusion. Fusion is executed by gB, gH, gL. gH is likely to be the real fusion glycoprotein, as its ectodomain carries a -helix with attributes of an internal fusion peptide, and two coiled coil heptad repeats. As far as HSV egress is concerned, controversy still exists about the possible routes of egress (luminal versus de-envelopment re-envelopment). A growing consensus in favor of the latter rests on studies of tegument assembly and the possible role of non essential glycoproteins in the cytoplasmic re-envelopment. is discussed. The lines of evidence in favor of, or against each route, as well as a novel possible route of egress are discussed.