Interaction of glycoprotein gIII with a cellular heparinlike substance mediates adsorption of pseudorabies virus

Glycoprotein gIII is one of the major envelope glycoproteins of pseudorabies virus (PrV) (Suid herpesvirus 1). Although it is dispensable for viral growth, it has been shown to play a prominent role in the attachment of the virus to target cells, since gIII- deletion mutants are severely impaired in adsorption (C. Schreurs, T. C. Mettenleiter, F. Zuckermann, N. Sugg, and T. Ben-Porat, J. Virol. 62:2251-2257, 1988). We show here that during the process of adsorption of PrV, the viral glycoprotein gIII interacts with a cellular heparinlike receptor. This conclusion is based on the following findings. (i) Heparin inhibits plaque formation of PrV by preventing the adsorption of wild-type virions to target cells. However, heparin does not interfere with the plaque formation of PrV mutants that lack glycoprotein gIII. (ii) Wild-type virions readily adsorb to matrix-bound heparin, whereas gIII- mutants do not. (iii) Pretreatment of cells with heparinase reduces considerably the ability of wild-type PrV to adsorb to these cells and to form plaques but does not negatively affect gIII- mutants. (iv) Glycoprotein gIII binds to heparin and appears to do so in conjunction with glycoprotein gII. Although heparin significantly reduces the adsorption of wild-type virus to all cell types tested, quantitative differences in the degree of inhibition of virus adsorption by heparin to different cell types were observed. Different cell types also retain their abilities to adsorb wild-type PrV to a different extent after treatment with heparinase and differ somewhat in their relative abilities to adsorb gIII- mutants. Our results show that while the primary pathway of adsorption of wild-type PrV to cells occurs via the interaction of viral glycoprotein gIII with a cellular heparinlike receptor, an alternative mode of adsorption, which is not dependent on either component, exists. Furthermore, the relative abilities of different cell types to adsorb PrV by the gIII-dependent or the alternative mode vary to some extent.