We present the nucleotide sequence of a region from the genome of the A + T-rich gammaherpesvirus, herpesvirus saimiri (HVS), which includes the coding sequences for the viral thymidine kinase (TK) gene. The organization of genes in this region resembles the homologous region of the Epstein-Barr virus (EBV) genome and is very compact, using overlapping coding sequences and with nucleotides shared by initiation and termination codons of neighbouring reading frames. The HVS TK is predicted to contain a 527 residue polypeptide with the first part of the presumptive nucleotide-binding site [(L, I, V)(F, Y)(I, L)(D, E)(G)(X)(X)(G)(L, I, V, M)(G)(K)(T, S)(T, S)] located at residues 212 to 224. This motif is close to the amino terminus of the TK polypeptides of alphaherpesviruses and the polypeptides of the cellular and poxvirus-encoded enzymes. The corresponding reading frame of the human gammaherpesvirus (EBV) also has a long amino-terminal extension but significant amino acid sequence similarities between the HVS and EBV sequences are not observed until the region of the nucleotide-binding site. Comparisons of these homologous carboxy-terminal sequences of the HVS- and EBV-encoded proteins with those from six alphaherpes viruses and proteins encoded by Marek's disease virus (MDV) and the herpesvirus of turkeys (HVT) confirm that the HVS and EBV sequences are products of a distinct lineage. The sequences of the MDV and HVT encoded enzymes are significantly more similar to sequences of alphaherpesvirus enzymes than to those of HVS and EBV. Comparison of these 10 highly divergent TK sequences extends and refines the identification of essential features of this family of herpesvirus enzymes and defines 19 positions at which all sequences have identical residues.


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