BINDING OF HERPES-SIMPLEX VIRUS TO CELLULAR HEPARAN-SULFATE, AN INITIAL STEP IN THE ADSORPTION PROCESS

It has been suggested that heparan sulphate has a receptor function in the initial phase of the attachment of herpes simplex virus (HSV) to cells. We have studied the influence of glycosaminoglycans on cell adsorption of, and plaque formation by, HSV-1 and HSV-2, with regard to the role of saccharide structure, chain length and charge density. Heparin and highly-sulphated heparan sulphate (1.5 sulphate groups/disaccharide unit), but neither chondroitin sulphate nor dermatan sulphate, were found to compete with the cellular receptor for attachment of HSV. Heparan sulphate preparations of low sulphate content (0.5 and 0.7 sulphate groups/disaccharide unit) failed to show any significant interaction with HSV. Oligosaccharides generated by partial deaminative cleavage of heparin were used to determine the minimum molecular size required for the binding of virus; the smallest oligosaccharide which reacted with HSV was composed of 10 monosaccharide units. The importance of charge density was demonstrated more directly by subfractionation of the heparin dodecasaccharide fraction by anion-exchange HPLC. The virus-binding capacities of the four resulting dodecasaccharide subfractions increased from the least sulphated to the most heavily sulphated fraction. The results reported are discussed in relation to virus-receptor interactions involved in the attachment of HSV, including the reported binding of HSV to the fibroblast growth factor receptor.