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Role of viral ribonucleotide reductase in the increase of dTTP pool size in herpes simplex virus-infected Vero cells

Laboratory of Virology, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Nagoya 466, Japan

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.

Received 6 June 1990; accepted 14 February 1991.