title: Cyclosporin A resistance of herpes simplex virus-induced "fusion from within" as a phenotypical marker of mutations in the Syn 3 locus of the glycoprotein B gene.
abstract: We here report research in which nine strains of Herpes simplex virus (HSV) with fusing activity were investigated in order to establish precise phenotypical markers of mutations in the carboxy terminus of glycoprotein B (gB). The gene region encoding the carboxy terminus of gB was isolated, then cloned, and finally sequenced. Our investigation showed that seven strains have different mutations in the syn 3 locus. We observed no base difference in the gB gene region encoding the carboxy terminus of gB of two other strains. Strains with a mutation in the carboxy terminus of gB induced fusion from within (FFWI) in the presence of Cyclosporin A (CyA) at a concentration up to 150 microM. There are two clusters of mutations correlated with the syn 3 locus and selected in the presence of CyA: One group comprised of amino acid substitutions at position 816, the other of changes at positions 853, 854, and 857. In contrast, the fusion induced by strains with mutations in other syn loci is CyA sensitive. CyA inhibits the FFWI at concentrations of 20-60 microM. The results demonstrate the CyA resistance of HSV-induced FFWI should serve as a phenotypical marker of mutations in the carboxy terminus of gB. Moreover, our investigations revealed that fusion from without (FFWO) does not always serve as a phenotypical marker of mutations in the syn 3 locus. On the one hand, all FFWO-positive strains possess a syn 3 locus mutation, whilst, on the other hand, five strains with mutations in the carboxy terminus of gB are FFWO negative.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Division of Experimental Virology, Johannes Gutenberg University, Mainz, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Walev
authors.forename: M
authors.initials: M
authors.lastname: Lingen
authors.forename: M
authors.initials: M
authors.lastname: Lazzaro
authors.forename: K
authors.initials: K
authors.lastname: Weise
authors.forename: D
authors.initials: D
authors.lastname: Falke
mesh_terms: D000818:Animals; D002459:Cell Fusion / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D016572:Cyclosporine / Q000494:pharmacology; D004352:Drug Resistance, Microbial / Q000235:genetics; D005814:Genes, Viral; D005819:Genetic Markers; D006801:Humans; D009154:Mutation; D010641:Phenotype; D018139:Simplexvirus / Q000187:drug effects / Q000235:genetics*; D014759:Viral Envelope Proteins / Q000235:genetics*; D014760:Viral Fusion Proteins / Q000235:genetics
chemical_list: D005819:Genetic Markers; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins; D016572:Cyclosporine