Varicella-zoster virus specifies a thymidylate synthetase

A homology search of proteins predicted from the recently reported complete DNA sequence of varicella-zoster virus (VZV) revealed that the product of gene 13 was highly homologous to eukaryotic and prokaryotic thymidylate synthetases (TSs). The VZV protein was shown to be a TS by three functional tests. Firstly, a plasmid designed to express the native protein was able to complement a strain of Escherichia coli in which the natural TS gene is deleted. Secondly, in an enzyme assay for TS, extracts of the complemented strain were capable of releasing tritiated water from 2'-deoxy[5-3H]uridylate. Thirdly, these extracts contained a protein that bound isotopically labelled 5-fluoro-2'-deoxyuridylate, a ligand specific for the active site of TS. In addition, a novel ligand-binding protein was detected in human cells infected with VZV.