Interaction of Polylysine with the Cellular Receptor for Herpes Simplex Virus Type 1

Abstract

SUMMARYWe earlier reported that neomycin blocked reversibly the binding of herpes simplex virus type 1 (HSV-1) to the receptor of BHK cells, while the binding of HSV-2 to the receptor was unaffected. We could not determine whether the effect was on the virus particle, the receptor, or both. We have now tested several other cationic substances, and report that polylysine (and polyarginine) block the binding of HSV-1 to the receptor by interfering with the cellular receptor function; higher molecular weight polylysines were more potent than those of lower molecular weight. Polylysine and neomycin showed additive effects. In vitro, polylysine showed the same strong binding to the plasma membrane phosphoinositides as did neomycin. Together these data suggest that the drugs may have a common target in the cell membrane. The HSV-1 and HSV-2 virus particles were unaffected by the drugs, as was the cellular HSV-2 receptor.

Binding of herpes simplex virus to cellular heparan sulphate, an initial step in the adsorption process

“…3(b). A somewhat stronger affinity was noted for HSV-2 with more efficient binding, but it seems doubtful that this discrepancy would be sufficiently large to explain the observed differences in receptor affinity (Addison et al, 1984;Vahlne et al, 1979) and sensitivity to competition by polycationic compounds (Langeland et al, 1988). However, as pointed out first by WuDunn & Spear (1989), attachment to heparan sulphate probably represents only the initial step in the anchoring of the virion to the plasma membrane.…”

“…Most mammalian cells carry heparan sulphate as a plasma membrane constituent (Kjell6n et al, 1981;H66k et al, 1984;Lane et al, 1984) and it has been claimed that the anionic heparan sulphate can function as a cellular receptor in the initial surface interactions of HSV and the cell (WuDunn & Spear, 1989). This statement is supported by observations that enzymic digestion of the cell surface heparan sulphate reduces the binding of HSV to cells (WuDunn & Spear, 1989) and that the cationic aminoglycosides neomycin and polylysine block the binding of HSV to its cell receptor (Langeland et al, 1987(Langeland et al, , 1988. The blocking probably results from competition between the virus and the cationic compound.…”

“…Whether HSV-1 and HSV-2 interfere with each other at the cell surface level has been a matter of debate (Addison et al, 1984;Langeland et al, 1988;Vahlne et al, 1979;WuDunn & Spear, 1989) and it has not been determined whether the two types utilize the same or different receptor structures. Both HSV-1 and HSV-2 bind to heparan sulphate (WuDunn & Spear, 1989), but whereas neomycin reversibly blocks the binding of HSV-1 to cells, the attachment of HSV-2 is unaffected (Langeland et al, 1988), suggesting typespecific differences in the interactions of the virus and its cellular receptors.…”

“…Both HSV-1 and HSV-2 bind to heparan sulphate (WuDunn & Spear, 1989), but whereas neomycin reversibly blocks the binding of HSV-1 to cells, the attachment of HSV-2 is unaffected (Langeland et al, 1988), suggesting typespecific differences in the interactions of the virus and its cellular receptors.…”

A Small Molecule Mimicking a Phosphatidylinositol (4,5)-Bisphosphate Binding Pleckstrin Homology Domain

“…Taking all these observations together, it is evident that PHDM is a potent chemical receptor that both compounds bind to phosphatidylserine, phosphatidylinositol and phosphatidylinositol monophosphate (37). These two binding agents are therefore not ideal to study PI(4,5)P 2 -dependent functions.…”