Herpesvirus ateles gene product Tio interacts with nonreceptor protein tyrosine kinases

Herpesvirus ateles is a gamma-2-herpesvirus which naturally infects spider monkeys (Ateles spp.) and causes malignant lymphoproliferative disorders in various other New World primates. The genomic sequence of herpesvirus atel es strain 73 revealed a close relationship to herpesvirus saimiri, with a h igh degree of variability within the left terminus of the coding region. A spliced mRNA transcribed from this region was detected in New World monkey T-cell lines transformed by herpesvirus ateles in vitro or derived from T c ells of infected Saguinus oedipus. The encoded viral protein, termed Tie, s hows restricted homology to the oncoprotein StpC and to the tyrosine kinase -interacting protein Tip, two gene products responsible for the T-cell-tran sforming and oncogenic phenotype of herpesvirus saimiri group C strains. Ti o was detectable in lysates of the transformed T lymphocytes. Dimer formati on was observed after expression of recombinant Tie. After cotransfection, Tio aas phosphorylated in vivo by the protein tyrosine kinases Lck and Src and less efficiently by Fyn. Stable complexes of these Src family kinases w ith the viral protein were detected in lysates of the transfected cells. Bi nding analyses indicated a direct interaction of Tio with the SH3 domains o f Lyn, Hck, Lck, Src, Fyn, and Yes. In addition, tyrosine-phosphorylated Ti o bound to the SH2 domains of Lck, Src, or Fyn. Thus, herpesvirus ateles-en coded Tio may contribute to viral T-cell transformation by influencing the function of Src family kinases.