The hepatitis C virus Core protein is a potent nucleic acid chaperone that directs dimerization of the viral(+) strand RNA in vitro
The hepatitis C virus Core protein is a potent nucleic acid chaperone that directs dimerization of the viral(+) strand RNA in vitro
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DOI：
10.1093/nar/gkh579
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发表时间：
2004-04-01
影响因子：
14.9
通讯作者：
Darlix, JL
中科院分区：
文献类型：
--
作者：
Cristofari, G;Ivanyi-Nagy, R;Darlix, JL
丙型肝炎病毒是引起慢性肝炎、肝硬变和肝细胞癌的重要人类病原体。丙型肝炎病毒是一种有包膜的病毒，具有阳性的单链RNA基因组，编码单一的多蛋白，该多蛋白被加工成病毒蛋白。数百个结构核心蛋白分子被认为覆盖在病毒颗粒中的基因组，就像逆转录病毒中的核衣壳(NC)蛋白分子一样，逆转录病毒是另一类包含正义RNA基因组的包膜病毒。逆转录病毒NC蛋白还具有核酸伴侣性质，在逆转录病毒复制过程中基因组的结构重构中发挥关键作用。丙型肝炎病毒核心蛋白和逆转录病毒NC蛋白之间的这种相似促使我们研究了丙型肝炎病毒核心蛋白假定的核酸伴侣特性。在这里，我们报道了核心蛋白伴随互补的DNA和RNA序列的退火，以及通过链交换形成最稳定的双链。这些结果表明，丙型肝炎病毒核心蛋白是一种类似于逆转录病毒NC蛋白的核酸伴侣。我们还发现，核心蛋白指导丙型肝炎病毒(+)RNA3‘非翻译区的二聚化，该区域由一个保守的回文序列推动，可能参与病毒复制的几个阶段。
The hepatitis C virus (HCV) is an important human pathogen causing chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. HCV is an enveloped virus with a positive-sense, single-stranded RNA genome encoding a single polyprotein that is processed to generate viral proteins. Several hundred molecules of the structural Core protein are thought to coat the genome in the viral particle, as do nucleocapsid (NC) protein molecules in Retroviruses, another class of enveloped viruses containing a positive-sense RNA genome. Retroviral NC proteins also possess nucleic acid chaperone properties that play critical roles in the structural remodelling of the genome during retrovirus replication. This analogy between HCV Core and retroviral NC proteins prompted us to investigate the putative nucleic acid chaperoning properties of the HCV Core protein. Here we report that Core protein chaperones the annealing of complementary DNA and RNA sequences and the formation of the most stable duplex by strand exchange. These results show that the HCV Core is a nucleic acid chaperone similar to retroviral NC proteins. We also find that the Core protein directs dimerization of HCV (+) RNA 3' untranslated region which is promoted by a conserved palindromic sequence possibly involved at several stages of virus replication.