Analysis of mutations in the thymidine kinase gene of varicella zoster virus associated with resistance to 5-iodo-2'-deoxyuridine and 5-bromo-2'-deoxyuridine.
We have analyzed mutations in the thymidine kinase (TK) gene of varicella zoster virus (VZV) which showed resistance to 5-iodo-2'-deoxyuridine (IDU) and 5-bromo-2'-deoxyuridine (BrDU). Through sequencing of the TK gene, we found three amino acids were exchanged (41 Asn-->Ser, 266 Cys-->Ile, 288 Ser-->Leu). These mutations were not located at either the nucleoside- or the ATP-binding site. This result suggests that the resistance to IDU and BrDU in this particular strain is due to the change in conformation of TK rather than the replacement of amino acids in the binding sites.
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D001483:Base Sequence; D001973:Bromodeoxyuridine / Q000494:pharmacology*; D017931:DNA Primers; D004279:DNA, Viral / Q000032:analysis; D004351:Drug Resistance; D014645:Herpesvirus 3, Human / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D007065:Idoxuridine / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009154:Mutation; D017354:Point Mutation; D013937:Thymidine Kinase / Q000235:genetics* / Q000378:metabolism
D000596:Amino Acids; D017931:DNA Primers; D004279:DNA, Viral; D013937:Thymidine Kinase; D001973:Bromodeoxyuridine; D007065:Idoxuridine