Characterization of a neurovirulent aciclovir-resistant variant of herpes simplex virus.
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.
Grey
Finn
F
Division of Virology, Department of Pathology, Cambridge University, Tennis Court Road, Cambridge CB2 1QP, UK.
Sowa
Mike
M
GlaxoSmithKline, UK Virology Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.
Collins
Peter
P
GlaxoSmithKline, UK Virology Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.
Fenton
Rob J
RJ
GlaxoSmithKline, UK Virology Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.
Harris
Wendy
W
GlaxoSmithKline, UK Virology Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.
Snowden
Wendy
W
GlaxoSmithKline, UK Virology Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.
Efstathiou
Stacey
S
Division of Virology, Department of Pathology, Cambridge University, Tennis Court Road, Cambridge CB2 1QP, UK.
Darby
Graham
G
GlaxoSmithKline, UK Virology Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.
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
D000998:Antiviral Agents; D004279:DNA, Viral; D013937:Thymidine Kinase; D000212:Acyclovir