Roles of thymidylate synthetase activity in herpes simplex virus-infected HeLa cells.

Thymidylate synthetase was not essential for herpes simplex virus replication. However, it appeared to contribute to the formation of a portion of thymidine nucleotides for DNA synthesis in virus-infected cells. Therefore, it is possible that the enzyme plays an important role in determining the potency of several selective antiviral thymidine analogs. Since synergistic effects of 5-fluoro-2'-deoxyuridine with other analogs on virus reproduction were observed, it is suggested that the effects of these analogs depend to a certain degree on the abilities of the monophosphate derivatives to inhibit thymidylate synthetase.