Effects of mutations on herpes simplex virus 1 thymidine kinase functionality: an in vitro assay based on detection of monophosphate forms of acyclovir and thymidine using HPLC/DAD

Antiviral Res. 2012 Sep;95(3):224-8. doi: 10.1016/j.antiviral.2012.07.001. Epub 2012 Jul 14.

Abstract

Discrimination between the mutations responsible for drug resistance and those of UL23 TK gene polymorphism can be difficult. A non-isotopic method has been developed to assess TK functionality by measuring monophosphate forms of both acyclovir (ACV) and thymidine using HPLC/DAD. Phenotypes of TKs could thus be characterized as TK altered (P84L, A189V, L227F), TK deficient (G200S, L291P) or TK partial (R163H). A reliable link between HSV UL23 TK mutations and ACV resistance is necessary for developing a powerful genotyping tool to detect ACV resistance quickly in clinical samples.

MeSH terms

  • Acyclovir / metabolism*
  • Antiviral Agents / metabolism*
  • Chromatography, High Pressure Liquid
  • Genotype
  • Herpesvirus 1, Human / drug effects
  • Herpesvirus 1, Human / enzymology*
  • Humans
  • Microbial Sensitivity Tests / methods
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism
  • Mutation, Missense*
  • Thymidine / metabolism*
  • Thymidine Kinase / genetics
  • Thymidine Kinase / metabolism*
  • Viral Proteins / genetics
  • Viral Proteins / metabolism*

Substances

  • Antiviral Agents
  • Mutant Proteins
  • Viral Proteins
  • Thymidine Kinase
  • Thymidine
  • Acyclovir