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Journal of Virology, June 1999, p. 4631-4639, Vol. 73, No. 6
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Herpesvirus Ateles Gene Product Tio Interacts with Nonreceptor Protein Tyrosine Kinases

Jens-Christian Albrecht,1,* Ute Friedrich,1 Christian Kardinal,2 Jadranka Koehn,1 Bernhard Fleckenstein,1 Stephan M. Feller,2 and Brigitte Biesinger1

Institut für Klinische und Molekulare Virologie, Universität Erlangen-Nürnberg, 91054 Erlangen,1 and Institut für Medizinische Strahlenkunde und Zellforschung, Universität Würzburg, 97078 Würzburg,2 Germany

Received 23 November 1998/Accepted 10 March 1999

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 ateles strain 73 revealed a close relationship to herpesvirus saimiri, with a high 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 cells of infected Saguinus oedipus. The encoded viral protein, termed Tio, shows restricted homology to the oncoprotein StpC and to the tyrosine kinase-interacting protein Tip, two gene products responsible for the T-cell-transforming and oncogenic phenotype of herpesvirus saimiri group C strains. Tio was detectable in lysates of the transformed T lymphocytes. Dimer formation was observed after expression of recombinant Tio. After cotransfection, Tio was phosphorylated in vivo by the protein tyrosine kinases Lck and Src and less efficiently by Fyn. Stable complexes of these Src family kinases with the viral protein were detected in lysates of the transfected cells. Binding analyses indicated a direct interaction of Tio with the SH3 domains of Lyn, Hck, Lck, Src, Fyn, and Yes. In addition, tyrosine-phosphorylated Tio bound to the SH2 domains of Lck, Src, or Fyn. Thus, herpesvirus ateles-encoded Tio may contribute to viral T-cell transformation by influencing the function of Src family kinases.

* Corresponding author. Mailing address: Institut für Klinische und Molekulare Virologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schlossgarten 4, D-91054 Erlangen, Germany. Phone: 49-9131-8526483. Fax: 49-9131-8526493. E-mail: jsalbrec{at}viro.med.uni-erlangen.de.

Journal of Virology, June 1999, p. 4631-4639, Vol. 73, No. 6
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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