title: Characterization of a neurovirulent aciclovir-resistant variant of herpes simplex virus.
abstract: A clinical isolate of herpes simplex virus type 1 that is aciclovir resistant but neurovirulent in mice was described previously. The mutation in this virus is a double G insertion in a run of seven G residues that has been shown previously to be a mutational hotspot. Using a sensitive assay, it has been demonstrated that preparations of this virus are able to induce low but consistent levels of thymidine kinase (TK) activity. However, this activity results from a high frequency mutational event that inserts a further G into the 'G-string' motif and thus restores the TK open reading frame. Passage of this virus through the nervous system of mice results in the rapid selection of the TK-positive variant. Thus, this variant is the major component in virus reactivated from latently infected ganglia. Mutation frequency appears to be influenced by the genetic background of the virus.
authors.affiliation: Division of Virology, Department of Pathology, Cambridge University, Tennis Court Road, Cambridge CB2 1QP, UK.
authors.forename: Finn
authors.initials: F
authors.lastname: Grey
authors.affiliation: GlaxoSmithKline, UK Virology Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.
authors.forename: Mike
authors.initials: M
authors.lastname: Sowa
authors.affiliation: GlaxoSmithKline, UK Virology Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Collins
authors.affiliation: GlaxoSmithKline, UK Virology Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Fenton
authors.affiliation: GlaxoSmithKline, UK Virology Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.
authors.forename: Wendy
authors.initials: W
authors.lastname: Harris
authors.affiliation: GlaxoSmithKline, UK Virology Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.
authors.forename: Wendy
authors.initials: W
authors.lastname: Snowden
authors.affiliation: Division of Virology, Department of Pathology, Cambridge University, Tennis Court Road, Cambridge CB2 1QP, UK.
authors.forename: Stacey
authors.initials: S
authors.lastname: Efstathiou
authors.affiliation: GlaxoSmithKline, UK Virology Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.
authors.forename: Graham
authors.initials: G
authors.lastname: Darby
mesh_terms: D000212:Acyclovir / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001483:Base Sequence; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D004279:DNA, Viral / Q000235:genetics; D024882:Drug Resistance, Viral; D016368:Frameshift Mutation; D017950:Ganglia, Sensory / Q000821:virology; D014644:Genetic Variation; D005838:Genotype; D006561:Herpes Simplex / Q000821:virology; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D009154:Mutation; D016366:Open Reading Frames; D010641:Phenotype; D014176:Protein Biosynthesis; D013937:Thymidine Kinase / Q000235:genetics; D014709:Vero Cells; D014774:Virulence / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D013937:Thymidine Kinase; D000212:Acyclovir