Glycosaminoglycan chains on cell surface proteoglycans provide initial docking sites for the binding to eukaryotic cells of various viruses and other microorganisms. The ubiquitously expressed glycosaminoglycan heparan sulfate is particularly important in this regard, at least for viruses. Often, binding of a viral protein to heparan sulfate is only the first step in a cascade of interactions between virus and cell that is required for viral entry into the cell and the initiation of infection. The steps that occur after binding of virus to heparan sulfate may require the interaction of other viral proteins with other cell surface molecules.

Several of the human herpesviruses, the focus of this Perspective, can make their initial contact with cells by binding to cell surface heparan sulfate. One member of this group, herpes simplex virus type 1 (HSV-1), can also bind to specific sites in heparan sulfate to trigger the fusion between viral envelope and cell membrane that is required for viral entry.