Effect of viral infections on the activity of cellular RNAs

早期的研究揭示了细胞RNA结合蛋白（RBP）NF 90/NFAR-1参与正链RNA病毒HCV（人丙型肝炎病毒）的复制。最近显示NF 90稳定并促进血管内皮生长因子（VEGF A）和促分裂原活化蛋白激酶磷酸酶（MKP-1）的mRNA的表达。病毒RNA隔离RBP的有趣场景指导了我们的工作假设，即HCV复制应该影响RBP调节的细胞mRNA的活性。我们证明了这种情况下，应用人肝癌细胞处理的应激诱导剂或转染HCV和黄病毒（西尼罗河，WNV）RNA，分别。MKP-1表达由应激和两种复制病毒RNA诱导。与此相反，VEGF mRNA的稳定性和VEGF的表达是专门增强HCV转染细胞。与这一发现一致，并且考虑到HCV感染触发肝细胞癌（HCC），HCV转染的肝癌细胞的肿瘤显示出比对照肿瘤显著更高程度的血管化。这一更新的目的是阐明VEGF mRNA的稳定性是如何在HCV感染的细胞中介导的，特别是了解NF 90和其他RBP在这一过程中的作用。

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.