Evidence for an interaction of herpes simplex virus with chondroitin sulfate proteoglycans during infection

Abstract

In a previous study, a mouse L cell mutant was isolated which is 90% resistant to HSV-1 infection (S. Gruenheid, L. Gatzke, H. Meadows, and F. Tufaro. J. Virol. 67, 93-100, 1993). This cell line, termed gro2C, failed to express heparan sulfate (HS)-glycosaminoglycans on the cell surface, which normally act as initial receptors for HSV-1 attachment to cultured cells. In this report, we extended the characterization of gro2C cells to explore the possibility that cell-surface chondroitin sulfate (CS) facilitates virus attachment to gro2C cells in the absence of HS. We found that soluble CS types A, B, and C strongly interfere with adsorption of HSV-1 to the surface of gro2C cells in a dose-dependent manner, and CS type B (dermatan sulfate) inhibited adsorption to parental (control) L cells by up to 10%. Moreover, gro2C cell infection was hypersensitive to inhibition by HS in comparison to control L cell infection. In all cases, a decrease in adsorption resulted in a decrease in infection. By contrast, the highly-sulfated glycosaminoglycan analog dextran sulfate was a relatively poor inhibitor of gro2C cell infection, indicating that the inhibitory effects of CS were related to its carbohydrate structure and not solely to its strong negative charge. By using a mutant virus strain which does not express the heparin-binding glycoprotein gC, we show that gC was not required for infection of gro2C cells, and was not required for the inhibition by HS or CS. Thus, the characterization of gro2C cell infection has revealed that one or more components of the HSV-1 particle can interact with cell-surface CS as well as HS to mediate infection of susceptible cells.