High-frequency phenotypic reversion and pathogenicity of an acyclovir-resistant herpes simplex virus mutant.
A double-guanine-insertion mutation within a run of guanines in the herpes simplex virus gene encoding thymidine kinase (TK) was previously found in an acyclovir-resistant clinical isolate. This mutation was engineered into strain KOS, and stocks were generated from single plaques. Plaque autoradiography revealed that most plaques in such stocks exhibited low levels of TK activity, while approximately 3% of plaques exhibited high levels of TK activity, indicating a remarkably high frequency of phenotypic reversion. This virus was able to reactivate from latency in mouse ganglia; a fraction of the reactivating virus expressed a high level of TK activity due to an additional G insertion, suggesting that the observed genetic instability contributed to pathogenicity.
Griffiths
Anthony
A
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Coen
Donald M
DM
D000212:Acyclovir / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D011995:Recombination, Genetic; D018139:Simplexvirus / Q000187:drug effects* / Q000235:genetics* / Q000472:pathogenicity; D013937:Thymidine Kinase / Q000235:genetics*; D014775:Virus Activation; D014779:Virus Replication
D000998:Antiviral Agents; D013937:Thymidine Kinase; D000212:Acyclovir