Characterization of a varicella-zoster virus variant with altered thymidine kinase activity.
A varicella-zoster virus (VZV) strain resistant to 5-iodo-2'-deoxyuridine (IdUrd) and 5-bromo-2'-deoxyuridine (BrdUrd) but sensitive to (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVdUrd) and (E)-5-(2-iodovinyl)-2'-deoxyuridine (IVdUrd) was isolated. The 2'-deoxythymidine (dThd) kinase of this mutant (Ito) strain was characterized; it was much less efficient in phosphorylating dThd, 2'-deoxycytidine, and BrdUrd than were the dThd kinases from wild-type (CaQu, Kobayashi) VZV strains. The Ito dThd kinase had a markedly decreased affinity for dThd, 2'-deoxycytidine, and BrdUrd but only a slightly decreased affinity for IVdUrd than had the wild-type VZV dThd kinase. BrdUrd was incorporated to a much lesser extent in VZV (Ito strain)-infected cells than wild-type VZV-infected cells, but IVdUrd was incorporated in Ito VZV-infected cells as efficiently as in wild-type VZV-infected cells. While resistant to IdUrd and BrdUrd, the Ito strain was susceptible to inhibitors of de novo thymidylate biosynthesis such as aminopterin.
D000630:Aminopterin / Q000494:pharmacology; D000998:Antiviral Agents / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D004591:Electrophoresis, Polyacrylamide Gel; D005467:Floxuridine / Q000494:pharmacology; D014645:Herpesvirus 3, Human / Q000201:enzymology*; D006801:Humans; D007065:Idoxuridine / Q000031:analogs & derivatives / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D010766:Phosphorylation; D013936:Thymidine / Q000378:metabolism; D013937:Thymidine Kinase / Q000378:metabolism*
D000998:Antiviral Agents; D005467:Floxuridine; C030360:5-(2-iodovinyl)-2'-deoxyuridine; D013937:Thymidine Kinase; D001973:Bromodeoxyuridine; D000630:Aminopterin; D007065:Idoxuridine; D013936:Thymidine