Biochemical basis for increased susceptibility to Cidofovir of herpes simplex viruses with altered or deficient thymidine kinase activity.
It has been observed that herpes simplex virus mutants with deficient or altered thymidine kinase activity are more susceptible to Cidofovir (CDV; 1-[(S)-3-hydroxy-2-(phosphonomethoxy)propyl]cytosine dihydrate) in tissue culture than are the parental strains. During infection of cells, the elevation of the dCTP pool by thymidine kinase mutant viruses is less than that induced by the wild-type virus. The competition between CDV diphosphate and dCTP at the viral polymerase is therefore changed in favor of CDV diphosphate, enhancing its activity.
Mendel
D B
DB
Department of Biochemistry and Virology, Gilead Sciences, Foster City, California 94404, USA.
Barkhimer
D B
DB
Chen
M S
MS
D000212:Acyclovir / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D005347:Fibroblasts; D006801:Humans; D009705:Nucleosides / Q000378:metabolism; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D018139:Simplexvirus / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics; D013937:Thymidine Kinase / Q000378:metabolism*; D010948:Viral Plaque Assay
D000998:Antiviral Agents; D009705:Nucleosides; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D003596:Cytosine; D013937:Thymidine Kinase; D000077404:Cidofovir; D000212:Acyclovir