Scheller Nicoletta, Mina Leonardo Bruno, Galão Rui Pedro, Chari Ashwin, Giménez-Barcons Mireia, Noueiry Amine, Fischer Utz, Meyerhans Andreas, Díez Juana
Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain.
Proc Natl Acad Sci U S A. 2009 Aug 11;106(32):13517-22. doi: 10.1073/pnas.0906413106. Epub 2009 Jul 23.
Inevitably, viruses depend on host factors for their multiplication. Here, we show that hepatitis C virus (HCV) RNA translation and replication depends on Rck/p54, LSm1, and PatL1, which regulate the fate of cellular mRNAs from translation to degradation in the 5'-3'-deadenylation-dependent mRNA decay pathway. The requirement of these proteins for efficient HCV RNA translation was linked to the 5' and 3' untranslated regions (UTRs) of the viral genome. Furthermore, LSm1-7 complexes specifically interacted with essential cis-acting HCV RNA elements located in the UTRs. These results bridge HCV life cycle requirements and highly conserved host proteins of cellular mRNA decay. The previously described role of these proteins in the replication of 2 other positive-strand RNA viruses, the plant brome mosaic virus and the bacteriophage Qss, pinpoint a weak spot that may be exploited to generate broad-spectrum antiviral drugs.
病毒不可避免地依赖宿主因子进行繁殖。在此，我们表明丙型肝炎病毒（HCV）的RNA翻译和复制依赖于Rck/p54、LSm1和PatL1，它们在5'-3'-腺苷酸化依赖性mRNA降解途径中调节细胞mRNA从翻译到降解的命运。这些蛋白质对高效HCV RNA翻译的需求与病毒基因组的5'和3'非翻译区（UTR）相关。此外，LSm1-7复合物与位于UTR中的必需顺式作用HCV RNA元件特异性相互作用。这些结果将HCV生命周期需求与细胞mRNA降解的高度保守宿主蛋白联系起来。这些蛋白质先前在另外两种正链RNA病毒（植物雀麦花叶病毒和噬菌体Qss）复制中的作用，指出了一个可能被利用来开发广谱抗病毒药物的弱点。
