Heparan sulfate glycosaminoglycans as primary cell surface receptors for herpes simplex virus

Our current incomplete picture of the earliest events in HSV infection may be summarized as follows. The initial interaction of virus with cells is the binding of virion gC to heparan sulfate moieties of cell surface proteoglycans. Stable binding of virus to cells may require the interaction of other virion glycoproteins with other cell surface receptors as well (including the interaction of gB with heparan sulfate). Penetration of virus into the cell is mediated by fusion of the virion envelope with the cell plasma membrane. Events leading up to this fusion require the action of at least three viral glycoproteins (gB, gD and gH), one or more of which may interact with specific cell surface components. It seems likely that binding of gB to cell surface heparan sulfate may occur and may be important in the activation of some event required for virus penetration. Heparan sulfate is present not only as a constituent of cell surface proteoglycans but also as a component of the extracellular matrix and basement membranes in organized tissues. In addition, body fluids contain both heparin and heparin-binding proteins, either of which can prevent the binding of HSV to cells (WuDunn and Spear, 1989). As a consequence, the spread of HSV infection is probably influenced, not only by immune responses to the virus, but also by the probability that virus will be entrapped or inhibited from binding to cells by extracellular forms of heparin or heparan sulfate.