Herpesvirus saimiri Oncoproteins Tip and StpC Synergistically Stimulate NF-κB Activity and Interleukin-2 Gene Expression

AbstractSaimiriine 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 poorly understood. It remains unclear how Tip and StpC affect gene expression and 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-κB and NF-AT, which is partially dependent on tyrosine phosphorylation