Systematische Untersuchung von Kombinationswirkungen der HHV-8-Gene auf die NF-κB-Aktivierung

Abstract

Activation of nuclear factor-kappa B (NF-κB), a key regulatory molecule in inflammation, is essential for survival of Human Herpesvirus (HHV)-8-infected cells. Using reverse transfection cell arrays (RTCA) as an unbiased systems biology approach the effects of all HHV-8-encoded genes individually and of pairwise combinations of all K- and latent genes on NF-κB-activation were investigated.

The strongest activations of NF-κB were observed with vFLIP and ORF75. Interestingly, some gene-combinations with vFLIP showed synergistic higher NF-κB-activation than vFLIP alone. ORF75 seems to activate NF-κB via the alternative pathway only.

Our results demonstrate that RTCA is a powerful tool to investigate combination effects of genes on different signal transduction pathways. We showed that vFLIP and ORF75 contribute to the robust NF-κB-activation observed in HHV-8-infected cells and that some genes can modulate the NF-κBactivation of vFLIP.