Role of RNA structures present at the 3′UTR of dengue virus on translation, RNA synthesis, and viral replication
Role of RNA structures present at the 3′UTR of dengue virus on translation, RNA synthesis, and viral replication
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DOI：
10.1016/j.virol.2005.06.009
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发表时间：
2005-09-01
期刊：
影响因子：
3.7
通讯作者：
Gamarnik, AV
中科院分区：
文献类型：
--
作者：
Alvarez, DE;Ezcurra, ALD;Gamarnik, AV
我们已经开发了一个登革热病毒复制子系统，可用于区分翻译和RNA复制。使用该系统，我们分析了登革病毒3'UTR处存在的明确定义的RNA元件在哺乳动物和蚊子细胞中的功能作用。我们的研究结果表明，3'UTR的单个结构域的缺失并没有显着影响输入RNA的翻译，但严重损害或废除RNA合成。我们证明了存在于基因组的5'和3'末端的序列之间的互补性对于登革病毒RNA合成是必不可少的，而3'UTR内的结构域A2或A3的缺失导致RNA扩增减少的复制子。我们还在复制子系统中表征了疫苗候选物rDEN2 Delta 30，并发现病毒减毒是由无效的RNA合成引起的。此外，使用复制子系统和重组病毒，我们鉴定了3'UTR的RNA区域，该区域增强登革病毒在BHK细胞中的复制，而在蚊子细胞中被复制。(c)2005年爱思唯尔公司All rights reserved.
We have developed a dengue virus replicon system that can be used to discriminate between translation and RNA replication. Using this system, we analyzed the functional role of well-defined RNA elements present at the 3'UTR of dengue virus in mammalian and mosquito cells. Our results show that deletion of individual domains of the 3'UTR did not significantly affect translation of the input RNA but seriously compromised or abolished RNA synthesis. We demonstrated that complementarity between sequences present at the 5' and 3' ends of the genome is essential for dengue virus RNA synthesis, while deletion of domains A2 or A3 within the 3'UTR resulted in replicons with decreased RNA amplification. We also characterized the vaccine candidate rDEN2 Delta 30 in the replicon system and found that viral attenuation is caused by inefficient RNA synthesis. Furthermore, using both the replicon system and recombinant viruses, we identified an RNA region of the 3'UTR that enhances dengue virus replication in BHK cells while is dispensable in mosquito cells. (c) 2005 Elsevier Inc. All rights reserved.