Effect of viral infections on the activity of cellular RNAs

• Applicant: Professor Dr. Sven-Erik Behrens
• Subject Area: Cell Biology
• Term: from 2007 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 33442413

Earlier studies revealed the participation of the cellular RNA binding protein (RBP) NF90/NFAR-1 in the replication of the positive-strand RNA virus HCV (human hepatitis C virus). NF90 was recently shown to stabilize and to promote the expression of the mRNAs of vascular endothelial growth factor (VEGF A) and of mitogen-activated protein kinase phosphatase (MKP-1). The intriguing scenario that viral RNAs sequester RBPs guided our working hypothesis that HCV replication should affect the activity of RBP-regulated cellular mRNAs. We proved this scenario applying human hepatoma cells that were treated with a stress-inducing agent or that were transfected with HCV and a flaviviral (West Nile, WNV) RNA, respectively. MKP-1 expression was induced by stress and both replicating viral RNAs. In contrast, VEGF mRNA stability and VEGF expression was exclusively enhanced in HCV transfected cells. In concert with this finding, and most relevant considering that HCV infection triggers hepatocel-lular carcinoma (HCC), tumors of HCV transfected hepatoma cells revealed a significantly higher degree of vascularisation than control tumors. This renewal aims at unravelling how VEGF mRNA stabilization is mediated in HCV infected cells and, in particular, to understand the role of NF90 and other RBPs in this process.

• DFG Programme: Research Units
• Subproject of: FOR 855: Cytoplasmic Regulation of Gene Expression