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鸭肝炎病毒 5'-UTR 具有与 HCV 相似的 IRES 活性,该活性独立于 eIF4F 复合物,并受下游编码序列的调节。

The duck hepatitis virus 5'-UTR possesses HCV-like IRES activity that is independent of eIF4F complex and modulated by downstream coding sequences.

机构信息

Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, PR China.

出版信息

Virol J. 2011 Mar 31;8:147. doi: 10.1186/1743-422X-8-147.

DOI:10.1186/1743-422X-8-147
PMID:21450110
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3072930/
Abstract

Duck hepatitis virus (DHV-1) is a worldwide distributed picornavirus that causes acute and fatal disease in young ducklings. Recently, the complete genome of DHV-1 has been determined and comparative sequence analysis has shown that possesses the typical picornavirus organization but exhibits several unique features. For the first time, we provide evidence that the 626-nucleotide-long 5'-UTR of the DHV-1 genome contains an internal ribosome entry site (IRES) element that functions efficiently both in vitro and in mammalian cells. The prediction of the secondary structure of the DHV-1 IRES shows significant similarity to the hepatitis C virus (HCV) IRES. Moreover, similarly to HCV IRES, DHV-1 IRES can direct translation initiation in the absence of a functional eIF4F complex. We also demonstrate that the activity of the DHV-1 IRES is modulated by a viral coding sequence located downstream of the DHV-1 5'-UTR, which enhances DHV-1 IRES activity both in vitro and in vivo. Furthermore, mutational analysis of the predicted pseudo-knot structures at the 3'-end of the putative DHV-1 IRES supported the presence of conserved domains II and III and, as it has been previously described for other picornaviruses, these structures are essential for keeping the normal internal initiation of translation of DHV-1.

摘要

鸭肝炎病毒(DHV-1)是一种分布广泛的小核糖核酸病毒,可导致雏鸭急性和致命疾病。最近,已确定 DHV-1 的完整基因组,比较序列分析表明其具有典型的小核糖核酸病毒结构,但表现出几个独特的特征。我们首次提供证据表明,DHV-1 基因组 626 个核苷酸长的 5'UTR 包含一个内部核糖体进入位点(IRES)元件,该元件在体外和哺乳动物细胞中均能有效发挥作用。DHV-1 IRES 的二级结构预测显示与丙型肝炎病毒(HCV)IRES 具有显著相似性。此外,与 HCV IRES 类似,DHV-1 IRES 可在缺乏功能性 eIF4F 复合物的情况下指导翻译起始。我们还证明,位于 DHV-1 5'UTR 下游的病毒编码序列可调节 DHV-1 IRES 的活性,从而在体外和体内均增强 DHV-1 IRES 的活性。此外,对推定的 DHV-1 IRES 3'末端预测假结结构的突变分析支持保守结构域 II 和 III 的存在,并且与其他小核糖核酸病毒先前描述的情况一样,这些结构对于保持 DHV-1 的正常内部翻译起始是必不可少的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0629/3072930/ffd5eca16fa0/1743-422X-8-147-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0629/3072930/cd5b547ffe23/1743-422X-8-147-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0629/3072930/133d719bd27c/1743-422X-8-147-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0629/3072930/e772f6056f12/1743-422X-8-147-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0629/3072930/af52b40b3e29/1743-422X-8-147-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0629/3072930/ffd5eca16fa0/1743-422X-8-147-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0629/3072930/cd5b547ffe23/1743-422X-8-147-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0629/3072930/133d719bd27c/1743-422X-8-147-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0629/3072930/e772f6056f12/1743-422X-8-147-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0629/3072930/af52b40b3e29/1743-422X-8-147-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0629/3072930/ffd5eca16fa0/1743-422X-8-147-6.jpg

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本文引用的文献

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Translation initiation factors are not required for Dicistroviridae IRES function in vivo.翻译起始因子对于双顺反子病毒科内部核糖体进入位点(IRES)在体内的功能并非必需。
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Divergent picornavirus IRES elements.不同的微小核糖核酸病毒内部核糖体进入位点元件
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The picornavirus avian encephalomyelitis virus possesses a hepatitis C virus-like internal ribosome entry site element.微小核糖核酸病毒禽脑脊髓炎病毒拥有一个丙型肝炎病毒样的内部核糖体进入位点元件。
Cleavage of poly(A)-binding protein by duck hepatitis A virus 3C protease.
多聚(A)结合蛋白的切割由鸭肝炎 A 病毒 3C 蛋白酶完成。
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A distinct group of hepacivirus/pestivirus-like internal ribosomal entry sites in members of diverse picornavirus genera: evidence for modular exchange of functional noncoding RNA elements by recombination.不同小RNA病毒属成员中一组独特的丙型肝炎病毒/瘟病毒样内部核糖体进入位点:通过重组进行功能性非编码RNA元件模块化交换的证据。
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