Thymidine kinase activity of ocular herpes simplex isolates resistant to IUDR therapy.
Thymidine kinase (TK) activity was examined in extracts of TK-deficient cells infected with low passage isolates of herpes simplex virus type 1 (HSV-1) obtained from patients with herpetic keratitis. TK activity induced by the virus, relative phosphorylation rates of thymidine and iododeoxyuridine (IUDR), and Km values for thymidine and for IUDR were compared for TK induced by the different viral isolates. Four of the five isolates showing IUDR resistance in vitro and in vivo also exhibited alterations in properties of the viral TK. Two induced very low levels of viral TK. Three (including one with reduced TK) had increased Km values for IUDR. A fifth IUDR-resistant isolate induced TK similar to the IUDR-sensitive isolates. The results indicate that modification of viral gene for TK may be responsible for development of clinical resistance to IUDR in many occurrences of herpetic keratitis.
D002460:Cell Line; D004352:Drug Resistance, Microbial; D006801:Humans; D007065:Idoxuridine / Q000378:metabolism / Q000627:therapeutic use*; D007635:Keratitis, Dendritic / Q000188:drug therapy / Q000201:enzymology*; D013379:Substrate Specificity; D013937:Thymidine Kinase / Q000378:metabolism*
D013937:Thymidine Kinase; D007065:Idoxuridine