title: Partial resistance to gD-mediated interference conferred by mutations affecting herpes simplex virus type 1 gC and gK.
abstract: 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 not binding. Previous studies have shown that mutations or variations in virion-associated gD can confer resistance to gD-mediated interference. Here we show that HSV-1 mutants selected for enhanced ability to bind and penetrate in the presence of inhibitory concentrations of heparin were partially resistant to gD-mediated interference. The resistance was largely due to the presence of two mutations: one in gC (the major heparin-binding glycoprotein) resulting in the absence of gC expression and the other in gK resulting in a syncytial phenotype. The results imply that heparin selected for mutants with altered postbinding requirements for entry. Resistance to gD-mediated interference conferred by mutations affecting gC and gK has not been previously described.
authors.affiliation: Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611, USA.
authors.forename: P E
authors.initials: PE
authors.lastname: Pertel
authors.forename: P G
authors.initials: PG
authors.lastname: Spear
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D014644:Genetic Variation; D006493:Heparin / Q000494:pharmacology; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006801:Humans; D016296:Mutagenesis; D016297:Mutagenesis, Site-Directed; D016133:Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000096:biosynthesis / Q000378:metabolism*; D014771:Virion / Q000502:physiology
chemical_list: C072448:UL53 protein, Human herpesvirus 1; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C050591:glycoprotein gG-1, herpes simplex virus type 1; D006493:Heparin