PARTIAL RESISTANCE TO GD-MEDIATED INTERFERENCE CONFERRED BY MUTATIONSAFFECTING HERPES-SIMPLEX VIRUS TYPE-1 GC AND GK

Cells expressing herpes simplex virus (HSV) gD can be resistant to HSV entry as a result of gD-mediated interference, HSV strains differ in sensitivity to this interference, which blocks viral penetration but n ot binding, Previous studies have shown that mutations or variations i n virion-associate go can confer resistance to go-mediated interferenc e, Here we show that HSV-1 mutants selected for enhanced ability to bi nd and penetrate in the presence of inhibitory concentrations of hepar in were partially resistant to gD-mediated interference, The resistanc e was largely due to the presence of two mutations: one in gC (the maj or heparin-binding glycoprotein) resulting in the absence of gC expres sion and the other in gK resulting in a syncytial phenotype. The resul ts imply that heparin selected for mutants with altered postbinding re quirements for entry. Resistance to gD-mediated interference conferred by mutations affecting gC and gK has not been previously described.