title: Characterization of herpes simplex virus type 1 thymidine kinase mutants selected under a single round of high-dose brivudin.
abstract: A broad variety of herpes simplex virus type 1 clones was selected under a single round of high-dose selection with brivudin. Mutations in the thymidine kinase (TK) genes consisted of 42% frameshift mutations within homopolymer repeats of G's and C's and single nucleotide substitutions (58%) that produced stop codons (Q261 and R281) or a new codon at the site of the substitution (A168T, R51W, G59W, G206R, R220H, Y239S, and T287 M). The A168T change, associated with an altered TK phenotype, proved to be the most commonly selected substitution. For the different mutants, a correlation between phenotype, genotype, and in vivo neurovirulence was observed.
authors.affiliation: Katholieke Universiteit Leuven, Rega Institute for Medical Research, Laboratory of Virology, Minderbroedersstraat 10, B-3000 Leuven, Belgium. graciela.andrei@rega.kuleuven.ac.be
authors.forename: Graciela
authors.initials: G
authors.lastname: Andrei
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Pierre
authors.initials: P
authors.lastname: Fiten
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.forename: Ghislain
authors.initials: G
authors.lastname: Opdenakker
authors.forename: Robert
authors.initials: R
authors.lastname: Snoeck
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001973:Bromodeoxyuridine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002522:Chlorocebus aethiops; D018388:Codon, Terminator; D024882:Drug Resistance, Viral; D016368:Frameshift Mutation; D008958:Models, Molecular; D010641:Phenotype; D012641:Selection, Genetic; D018139:Simplexvirus / Q000187:drug effects / Q000235:genetics*; D013937:Thymidine Kinase / Q000737:chemistry / Q000235:genetics*; D014709:Vero Cells
chemical_list: D000998:Antiviral Agents; D018388:Codon, Terminator; C020235:brivudine; D013937:Thymidine Kinase; D001973:Bromodeoxyuridine