Susceptibility of a herpes simplex virus ribonucleotide reductase null mutant to deoxyribonucleosides and antiviral nucleoside analogs.
A herpes simplex virus ribonucleotide reductase (RR) null mutant, ICP6 delta, exhibited hypersensitivity to hydroxyurea, and to the precursors of allosteric inhibitors of cellular RR. The mutant was also much more sensitive than the parental KOS to all of antiviral nucleoside analogs tested, including acyclovir (ACV), ganciclovir (DHPG) and BVaraU. Our data indicate that cellular RR is essential for the growth of ICP6 delta, and suggest that inhibitors of viral RR could act as potentiators of all of anti-herpetic nucleoside analogs whose targets are viral DNA polymerase.
Yamada
Y
Y
Laboratory of Virology, Nagoya University School of Medicine, Aichi.
Yamamoto
N
N
Daikoku
T
T
Nishiyama
Y
Y
D000212:Acyclovir / Q000494:pharmacology*; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000494:pharmacology; D003853:Deoxyribonucleosides / Q000494:pharmacology; D015774:Ganciclovir / Q000494:pharmacology*; D006918:Hydroxyurea / Q000494:pharmacology; D009154:Mutation; D019384:Nucleic Acid Synthesis Inhibitors; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors*; D018139:Simplexvirus / Q000187:drug effects* / Q000201:enzymology
D003853:Deoxyribonucleosides; D019384:Nucleic Acid Synthesis Inhibitors; D001086:Arabinofuranosyluracil; C031368:sorivudine; D012264:Ribonucleotide Reductases; D015774:Ganciclovir; D000212:Acyclovir; D006918:Hydroxyurea