DEXTRAN SULFATE CAN ACT AS AN ARTIFICIAL RECEPTOR TO MEDIATE A TYPE-SPECIFIC HERPES-SIMPLEX VIRUS-INFECTION VIA GLYCOPROTEIN-B

Herpes simplex virus (HSV) adsorption to host cells is mediated, at le ast in part, by the interaction of viral glycoproteins with cell surfa ce glycosaminoglycans such as heparan sulfate and chondroitin sulfate. To investigate the contribution of various cell surface components in the infection pathway, we isolated a mutant cell line, sog9, which is unable to synthesize glycosaminoglycans (B. W. Banfield, Y. Leduc, L. Esford, K. Schubert, and F. Tufaro, J. Virol. 69:3290-3298, 1995). Al though HSV-1 and HSV-2 infection of sog9 cells is diminished, the cell s are still infected at about 0.5% efficiency, which suggests that the se cells normally express at least one nonglycosaminoglycan receptor. In this report, we used sog9 cells to test whether glycosaminoglycan a nalogs, such as dextran sulfate (DS), could functionally substitute fo r cellular glycosaminoglycans to initiate HSV infection. We show that high-molecular-weight DS added either prior to or during inoculation s timulated HSV-1 but not HSV-2 infection by up to 35-fold; DS added aft er viral adsorption had no effect on infection efficiency. Moreover, D S stimulated HSV-1 infection at 4 degrees C, indicating that this comp ound impinged on an early, energy-independent step in infection. Using radiolabeled virus, we showed that HSV-1 is more efficient than HSV-2 in adsorbing to DS immobilized on microtiter wells. This raised the p ossibility that only HSV-1 could engage additional receptors to initia te infection in the presence of DS. To determine which viral component (s) facilitated DS stimulation, a panel of intertypic recombinants and deletion mutant viruses was investigated. These assays showed that DS stimulation of infection is mediated primarily by gB-1. Thus, this st udy provides direct evidence that a principal role for cell surface gl ycosaminoglycans in HSV infection is to provide an efficient matrix fo r virus adsorption. Moreover, by using DS as an alternative adsorption matrix (a trans receptor), we uncovered a functional, type-specific i nteraction of HSV-1 with a cell surface receptor.