Disease relevance of SaHV2gp71

• The A+T-rich genome of Herpesvirus saimiri contains a highly conserved gene for thymidylate synthase [1].
• We find no evidence for a virus-encoded thymidylate synthase activity (or a homology to a thymidylate synthase sequence) in G+C-rich representatives of alpha 1 (e.g., herpes simplex viruses, 66-68% G+C), beta (i.e., human cytomegalovirus, 58-59% G+C), and gamma 1 (i.e., Epstein-Barr virus, 60% G+C) herpesvirus subgroups [1].
• The TS gene of HVS occurs within a group of 5 genes that have no homologues in EBV [2].
• Herpesvirus saimiri codes, unlike most other herpesviruses, for a thymidylate synthase (TS) [3].
• Using degenerate PCR we identified a novel rhadinovirus, PapRV2, that has substantial sequence identity to two essential KSHV genes, the viral polymerase and thymidylate synthase [4].

High impact information on SaHV2gp71

• The predicted amino acid sequence of the 294-residue subunit of the virus enzyme is 70% homologous with the sequence of the human enzyme and about 50% homologous with prokaryotic thymidylate synthases, illustrating the remarkable structural constraints imposed by the thymidylate synthase function [1].
• These include thymidylate synthase, dihydrofolate reductase, complement control proteins, the cell surface antigen CD59, cyclins, and G protein-coupled receptors [5].
• Although TS is believed to be required for viral DNA synthesis, the TS-specific 2.5-kb mRNA was found most abundantly during the late phases of asynchronous virus replication in permissive cultures [6].
• To study the kinetics of gene activation, the TS promoter and regulatory sequences were cloned upstream of the chloramphenicol acetyltransferase (CAT) gene [6].
• This transcript is from the virus thymidylate synthase (TS) gene and its synthesis, like that of late mRNAs encoding the virus structural proteins, is sensitive to an inhibitor of virus DNA synthesis (phosphonoacetic acid, PAA) [7].

Biological context of SaHV2gp71

• The herpesvirus saimiri TS gene, which may be weakly transcribed during immediate early and early times of virus replication, is maximally expressed at the late phase [3].

Associations of SaHV2gp71 with chemical compounds

• The production of excess thymidylate by a virus thymidylate synthase in cells infected with an A+T-rich herpesvirus would provide one plausible source of biased mutations by the virus-encoded replicative enzymes, which we have previously suggested as the likely general cause of differences in the mean nucleotide compositions of herpesvirus genomes [1].

References