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

被引:20
|
作者
Malartre, Nicolas [1 ]
Boulieu, Roselyne [2 ,3 ]
Falah, Nisrine [4 ]
Cortay, Jean-Claude [4 ]
Lina, Bruno [1 ,4 ]
Morfin, Florence [1 ,4 ]
Frobert, Emilie [1 ,4 ]
机构
[1] Hosp Civils Lyon, Lab Virol Est, Ctr Biol & Pathol Est, Lyon, France
[2] Hosp Civils Lyon, Lab Pharmacocinet Clin, Hop Edouard Herriot, Lyon, France
[3] Univ Lyon 1, Pharm Clin, EA 4169, ISPB, F-69365 Lyon, France
[4] Univ Lyon 1, EMR 4610, Fac Med RTH Laennec, F-69365 Lyon, France
关键词
HSV1; Thymidine kinase; ACV resistance; HPLC/DAD; Genotyping; GENOTYPIC CHARACTERIZATION; DNA-POLYMERASE; PHENOTYPIC CHARACTERIZATION; TRANSPLANT RECIPIENTS; RESISTANT HSV-1; TYPE-1; STRAINS; GENE; CYTOMEGALOVIRUS; POLYMORPHISM;
D O I
10.1016/j.antiviral.2012.07.001
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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. (c) 2012 Elsevier B.V. All rights reserved.
引用
收藏
页码:224 / 228
页数:5
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