NF-kappaB activation by the viral oncoprotein StpC enhances IFN-gamma production in T cells.
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.
Glanz
Anja
A
Institute for Clinical and Molecular Virology, Friedrich-Alexander University Erlangen-Nuernberg, Erlangen, Germany.
Albrecht
Jens-Christian
JC
Heinemann
Stefanie
S
Fleckenstein
Bernhard
B
Isakov
Noah
N
Biesinger
Brigitte
B
D005786:Gene Expression Regulation; D017930:Genes, Reporter / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology*; D019169:Jurkat Cells; D016328:NF-kappa B / Q000378:metabolism*; D010750:Phosphoproteins / Q000276:immunology*; D054730:Protein Interaction Domains and Motifs / Q000276:immunology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology*
D016328:NF-kappa B; D010750:Phosphoproteins; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D014764:Viral Proteins; C092384:tyrosine kinase interacting protein, Saimiriine herpesvirus 2; D007371:Interferon-gamma