Herpes simplex virus (HSV) adsorption to host cells is mediated, at least in part, by the interaction of viral
glycoproteins with cell surface
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). Although HSV-1 and HSV-2
infection of sog9 cells is diminished, the cells are still infected at about 0.5% efficiency, which suggests that these cells normally express at least one nonglycosaminoglycan receptor. In this report, we used sog9 cells to test whether
glycosaminoglycan analogs, such as
dextran sulfate (DS), could functionally substitute for cellular
glycosaminoglycans to initiate HSV
infection. We show that high-molecular-weight DS added either prior to or during inoculation stimulated HSV-1 but not HSV-2
infection by up to 35-fold; DS added after viral adsorption had no effect on
infection efficiency. Moreover, DS stimulated HSV-1
infection at 4 degrees C, indicating that this compound 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 possibility that only HSV-1 could engage additional receptors to initiate
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 study provides direct evidence that a principal role for cell surface
glycosaminoglycans in HSV
infection is to provide an efficient matrix for virus adsorption. Moreover, by using DS as an alternative adsorption matrix (a trans receptor), we uncovered a functional, type-specific interaction of HSV-1 with a
cell surface receptor.