The Importance of Heparan Sulfate in Herpesvirus Infection

Herpes simplex virus type-1 (HSV-1) is one of many pathogens that use the cell surface glycosaminoglycan heparan sulfate as a receptor. Heparan sulfate is highly expressed on the surface and extracellular matrix of virtually all cell types making it an ideal receptor. Heparan sulfate interacts with HSV-1 envelope glycoproteins gB and gC during the initial attachment step during HSV-1 entry. In addition, a modified form of heparan sulfate, known as 3-O-sulfated heparan sulfate, interacts with HSV-1 gD to induce fusion between the viral envelope and host cell membrane. The 3-O-sulfation of heparan sulfate is a rare modification which occurs during the biosynthesis of heparan sulfate that is carried out by a family of enzymes known as 3-O-sulfotransferases. Due to its involvement in multiple steps of the infection process, heparan sulfate has been a prime target for the development of agents to inhibit HSV entry. Understanding how heparan sulfate functions during HSV-1 infection may not only be critical for inhibiting infection by this virus, but it may also be crucial in the fight against many other pathogens as well.