Analysis and characterization of the complete genome of tupaia (tree shrew) herpesvirus

The tupaia herpesvirus (THV) was isolated from spontaneously degenerating t issue cultures of malignant lymphoma, lung, and spleen cell cultures of tre e shrews (Tupaia spp.). The determination of the complete nucleotide sequen ce of the THV strain 2 genome resulted in a 195,857-bp-long, linear DNA mol ecule with a G+C content of 66.5%. The terminal regions of the THV genome a nd the loci of conserved viral genes were Pound to be G+C richer. Furthermo re, no large repetitive DNA sequences could be identified. This is in agree ment with the previous classification of THV as the prototype species of he rpesvirus genome group F. The search for potential coding regions resulted in the identification of 158 open reading frames (ORFs) regularly distribut ed on both DNA strands. Seventy-six out of the 158 ORFs code for proteins t hat are significantly homologous to known herpesvirus proteins. The highest homologies found were to primate and rodent cytomegaloviruses, Biological properties, protein homologies, the arrangement of conserved viral genes, a nd phylogenetic analysis revealed that THV is a member of the subfamily Bet aherpesvirinae. The evolutionary lineages of THV and the cytomegaloviruses seem to have branched off from a common ancestor. In addition, it was found that the arrangements of conserved genes of THV and murine cytomegalovirus strain Smith, both of which are not able to form genomic isomers, are coli near with two different human cytomegalovirus (HCMV) strain AD169 genomic i somers that differ from each other in the orientation of the long unique re gion. The biological properties and the high degree of relatedness of THV t o the mammalian cytomegaloviruses allow the consideration of THV as a model system for investigation of HCMV pathogenicity.