Herpesvirus saimiri oncoproteins Tip and StpC synergistically stimulate NF-KB activity and interleukin-2 gene expression

Saimiriine herpesvirus 2 (Herpesvirus saimiri) is capable of inducing lethal T-cell lymphoproliferative diseases in primates and of immortalizing human T lymphocytes in vitro. Two viral oncoproteins, Tip and StpC, are essential for T-cell transformation by Herpesvirus saimiri strains of the subgroup C, which exhibits a higher transformation potential than other subgroups of this virus. Despite the importance of these proteins, the molecular basis of their effects on T cells is pearly understood. It remains unclear how Ti p and StpC affect gene expression a nd what is the molecular basis of their cooperation. To address these issues, we expressed Tip and StpC in T lymphoblastoid cells and assessed both their effects on and transcription factors involved in IL-2 gene expression. Our study shows that Tip and StpC cooperate to upregulate IL-2 gene expression, that their effect is mediated primarily by NF-KB and NF-AT, which is partially dependent on tyrosine phosphorylation. (C) 2001 Academic Press.