NEOMYCIN INHIBITS GLYCOPROTEIN-C (GC)-DEPENDENT BINDING OF HERPES-SIMPLEX VIRUS TYPE-1 TO CELLS AND ALSO INHIBITS POSTBINDING EVENTS IN ENTRY

Previous studies have identified requirements for the binding of herpe s simplex virus type 1 (HSV-1) to cells, including the presence of par ticular glycoproteins in the Virion envelope (gC or gB) and the presen ce of particular glycosaminoglycan chains (principally heparan sulfate ) on cell surface proteoglycans. We show here that neomycin, a known i nhibitor of HSV infection, blocked early events in HSV infection by tw o mechanisms: partial inhibition of the gC-dependent. binding of virio ns, but not the g8-dependent binding, and inhibition of events that oc curred after the binding of virus to cells. Near-maximal (but incomple te) inhibition of virus binding occurred at low concentrations of neom ycin (1 mM) for wild-type and gB-negative virions only. Neomycin also inhibited the binding of isolated gC to cells at a similar concentrati on. Concentrations of neomycin as high as 50 mM had little or no effec t on the binding of gC-negative virions to cells. Nevertheless, neomyc in significantly inhibited infection by both wild-type and gC-negative virions, at concentrations greater than 10 mM, indicating that the in hibition at higher doses was not due to effects on virus binding. The effects of neomycin on virus binding suggest that gC (but not gB) and neomycin compete for binding to similar structural features of cell su rface heparan sulfate. (C) 1994 Academic Press, Inc.