Molecular Anatomy of Tupaia (Tree Shrew) adenovirus Genome; Evolution of Viral Genes and Viral Phylogeny

Adenoviruses are globally spread and infect species in all five taxons of vertebrates. Outstanding attention is focused on adenoviruses because of their transformation potential, their possible usability as vectors in gene therapy and their applicability in studies dealing with, e.g. cell cycle control, DNA replication, transcription, splicing, virus–host interactions, apoptosis, and viral evolution. The accumulation of genetic data provides the basis for the increase of our knowledge about adenoviruses. The Tupaia adenovirus (TAV) infects members of the genus Tupaiidae that are frequently used as laboratory animals in behavior research dealing with questions about biological and molecular processes of stress in mammals, in neurobiological and physiological studies, and as model organisms for human hepatitis B and C virus infections. In the present study the TAV genome underwent an extensive analysis including determination of codon usage, CG depletion, gene content, gene arrangement, potential splice sites, and phylogeny. The TAV genome has a length of 33,501 bp with a G+C content of 49.96%. The genome termini show a strong CG depletion that could be due to methylation of these genome regions during the viral replication cycle. The analysis of the coding capacity of the complete TAV genome resulted in the identification of 109 open reading frames (ORFs), of which 38 were predicted to be real viral genes. TAV was classified within the genus Mastadenovirus characterized by typical gene content, arrangement, and homology values of 29 conserved ORFs. Phylogenetic trees show that TAV is part of a separate evolutionary lineage and no mastadenovirus species can be considered as the most related. In contrast to other mastadenoviruses a direct ancestor of TAV captured a DUT gene from its mammalian host, presumably controlling local dUTP levels during replication and enhance viral replication in non-dividing host tissues. Furthermore, TAV possesses a second DNA-binding protein gene, that is likely to play a role in the determination of the host range. In view of these data it is conceivable that TAV underwent evolutionary adaptations to its biological environment resulting in the formation of special genomic components that provided TAV with the ability to expand its host range during viral evolution.