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.