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.
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.
Laboratoire de Virologie Est., Centre de Biologie et Pathologie Est., Hospices Civils de Lyon, Lyon, France.
Nicolas
N
Malartre
Roselyne
R
Boulieu
Nisrine
N
Falah
Jean-Claude
JC
Cortay
Bruno
B
Lina
Florence
F
Morfin
Emilie
E
Frobert
D000212:Acyclovir / Q000378:metabolism*; D000998:Antiviral Agents / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005838:Genotype; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D013936:Thymidine / Q000378:metabolism*; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D000998:Antiviral Agents; D050505:Mutant Proteins; D014764:Viral Proteins; D013937:Thymidine Kinase; D013936:Thymidine; D000212:Acyclovir