title: T-cell growth transformation by herpesvirus saimiri is independent of STAT3 activation.
abstract: Herpesvirus saimiri (saimirine herpesvirus 2) (HVS), a T-lymphotropic tumor virus, induces lymphoproliferative disease in several species of New World primates. In addition, strains of HVS subgroup C are able to transform T cells of Old World primates, including humans, to permanently growing T-cell lines. In concert with the Stp oncoprotein, the tyrosine kinase-interacting protein (Tip) of HVS C488 is required for T-cell transformation in vitro and lymphoma induction in vivo. Tip was previously shown to interact with the protein tyrosine kinase Lck. Constitutive activation of signal transducers and activators of transcription (STATs) has been associated with oncogenesis and has also been detected in HVS-transformed T-cell lines. Furthermore, Tip contains a putative consensus YXPQ binding motif for the SH2 (src homology 2) domains of STAT1 and STAT3. Tip tyrosine phosphorylation at this site was required for binding of STATs and induction of STAT-dependent transcription. Here we sought to address the relevance of STAT activation for transformation of human T cells by introducing a tyrosine-to-phenylalanine mutation in the YXPQ motif of Tip of HVS C488. Unexpectedly, the recombinant virus was still able to transform human T lymphocytes, but it had lost its capability to activate STAT3 as well as STAT1. This demonstrates that growth transformation by HVS is independent of STAT3 activation.
authors.affiliation: Institut für Klinische und Molekulare Virologie, Friedrich-Alexander Universität Erlangen-Nürnberg, Schlossgarten 4, D-91054 Erlangen, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Heck
authors.forename: Doris
authors.initials: D
authors.lastname: Lengenfelder
authors.forename: Monika
authors.initials: M
authors.lastname: Schmidt
authors.forename: Ingrid
authors.initials: I
authors.lastname: Müller-Fleckenstein
authors.forename: Bernhard
authors.initials: B
authors.lastname: Fleckenstein
authors.forename: Brigitte
authors.initials: B
authors.lastname: Biesinger
authors.forename: Armin
authors.initials: A
authors.lastname: Ensser
mesh_terms: D002472:Cell Transformation, Viral; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006567:Herpesvirus 2, Saimiriine / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D015534:Trans-Activators / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D010750:Phosphoproteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D014764:Viral Proteins; C092384:tyrosine kinase interacting protein, Saimiriine herpesvirus 2