The Role of HSV Glycoproteins in Mediating Cell Entry

The successful entry of herpes simplex virus (HSV) into a cell is a complex process requiring the interaction of several surface viral glycoproteins with host cell receptors. These viral glycoproteins are currently thought to work sequentially to trigger fusogenic activity, but the process is complicated by the fact that each glycoprotein is known to interact with a range of target cell surface receptor molecules. The glycoproteins concerned are gB, gD, and gH/gL, with at least four host cell receptor molecules known to bind to gB and gD alone. Redundancy among gD receptors is also evident and binding to both the gB and gD receptors simultaneously is known to be required for successful membrane fusion. Receptor type and tissue distribution are commonly considered to define the extent of viral tropism and thus the magnitude of pathogenesis. Viral entry receptors are therefore attractive pharmaceutical target molecules for the prevention and/or treatment of viral infections. However, the large number of HSV glycoprotein receptors makes a comprehensive understanding of HSV pathogenesis in vivo difficult. Here we summarize our current understanding of the various HSV glycoprotein cell surface receptors, define their redundancy and binding specificity, and discuss the significance of these interactions for viral pathogenesis.