Re-evaluation and in silico annotation of the Tupaia herpesvirus proteins

Herpesviruses represent an exceptionally suitable model to analyze evolutionary old pathogens, their competency to adapt to existing and changing molecular niches in host species, and the modulation of the gene content and function to comply with the requirements of life. The basis for numerous studies dealing with these questions are reliable statements about the gene content of herpesviral genomes and the functions of viral proteins. The recent determination of the coding strategy of the chimpanzee cytomegalovirus genome and the re-evaluation of the gene content of the human cytomegalovirus genome made it also necessary to restructure the putative transcription map of the Tupaia herpesvirus (THV) genome. Twenty-three THV-specific ORFs formerly predicted to be coding for viral proteins were deleted from the THV transcription map resulting in a gene layout that is now characterized by the presence of conserved genes in the genome center, that probably reflect the genome structure of common herpesviral ancestors, and species-specific genes at the termini. The conserved regions in the THV genome are characterized by high G + C contents between 60% and 80%, a high CpG dinucleotide frequency, and the presence of densely packed putative CpG islands. The genome termini seem to provide the requirements of large scale rearrangements and complements of the gene content to adapt to new environmental demands. With the help of the recently designed method of dictionary-driven, pattern-based protein annotation it was possible to assign putative functions to almost all potential THV proteins, e.g. 123 were found to be putative membrane or secreted proteins, putative signal domains were identified in 69, and 29 proteins were predicted to be glycosylated. The present study adds new aspects to the knowledge about the precise gene composition of herpesvirus genomes and viral protein functions that are of exceptional importance for studies dealing with the phylogeny, the evolution, vaccine vector development, virus-host interactions, pathogenesis and the determination of protein functions of herpesviruses.