- Interferon-gamma (IFN-gamma) is an essential regulator of innate and adaptive immune responses and a hallmark of the Th1 T-cell subset. It is produced at high levels by human T lymphocytes upon transformation with Herpesvirus saimiri, which depends on the expression of the viral oncoproteins saimiri transformation-associated protein of subgroup C (StpC) and tyrosine kinase-interacting protein (Tip). Here, we show that IFN-gamma production was induced by Tip in Jurkat T cells. StpC by itself did not affect IFN-gamma expression, but enhanced the effect of Tip. Our results substantiated the findings that StpC induces NF-kappaB activation and demonstrated that other transcription factors, including NFAT, AP-1 and serum response element regulators, were not activated by StpC in unstimulated T cells. Studies using StpC mutants deficient in NF-kappaB activation, dominant negative IkappaBalpha and constitutively active IKK2, established the importance of NF-kappaB in StpC-mediated upregulation of IFN-gamma production. These observations suggest that NF-kappaB induction by StpC contributes to the Th1-like phenotype of virus-transformed human T cells.