Role of viral ribonucleotide reductase in the increase of dTTP pool size in herpes simplex virus-infected Vero cells.
Infection of Vero cells with herpes simplex virus (HSV) causes a marked increase in the dTTP pool size of infected cells. In this study we examined the relative importance of the HSV-encoded ribonucleotide reductase (RR) and thymidine kinase (TK) in the increase of dTTP. In cells infected with an RR deletion mutant of HSV-1 strain KOS, there was no significant increase in the size of the dTTP pool, whereas the dTTP pool in HSV-1(TK-)-infected cells was increased in size to almost the same extent as that in HSV-1(TK+)-infected cells. Moreover, it was found that the increase in dTTP pool size was strongly inhibited by the addition of hydroxyurea, a specific inhibitor of RR, and 5-fluoro-2'-deoxyuridine, a specific inhibitor of thymidylate synthetase. These results suggest that the induction of viral RR is of primary importance in the increase of dTTP pool size in HSV-1-infected Vero cells.
Daikoku
T
T
Laboratory of Virology, Nagoya University School of Medicine, Japan.
Yamamoto
N
N
Maeno
K
K
Nishiyama
Y
Y
D000818:Animals; D002872:Chromosome Deletion; D005467:Floxuridine / Q000494:pharmacology; D006918:Hydroxyurea / Q000494:pharmacology; D007700:Kinetics; D010766:Phosphorylation; D012264:Ribonucleotide Reductases / Q000378:metabolism*; D018139:Simplexvirus / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D013936:Thymidine / Q000378:metabolism; D013942:Thymine Nucleotides / Q000378:metabolism*; D014709:Vero Cells; D014779:Virus Replication
D013942:Thymine Nucleotides; D005467:Floxuridine; D012264:Ribonucleotide Reductases; C024157:thymidine 5'-triphosphate; D013936:Thymidine; D006918:Hydroxyurea