Biological consequences of deletions within the 3′-untranslated region of flaviviruses may be due to rearrangements of RNA secondary structure
Biological consequences of deletions within the 3′-untranslated region of flaviviruses may be due to rearrangements of RNA secondary structure
复制标题
DOI：
10.1016/s0168-1702(99)00079-9
复制
发表时间：
1999-11-01
期刊：
影响因子：
5
通讯作者：
Holmes, EC
中科院分区：
文献类型：
--
作者：
Proutski, V;Gritsun, TS;Holmes, EC
此前有报道称，登革4型(DEN 4)病毒3‘-非翻译区(3’-UTR)的缺失被引入登革4型病毒(Men，R.，Bray，M.，Clark，D.，Chanock，R.M.，Lai，C.J.，1996)。包含RNA基因组3‘-非编码区缺失的DEN 4病毒突变体：细胞培养中的生长限制分析以及恒河猴病毒血症模式和免疫原性的改变。J.维罗尔。70,3930-3937)，壁虱传播脑炎(TBE)病毒(Mandl，C.W.，Holzmann，H.，Meixner，T.，Rauscher，S.，Stadler，P.F.，Allison，S.L.，Heinz，F.X，1998。TBE病毒3‘-非编码区的自发和工程缺失：构建高度减毒的黄病毒突变体。J.维罗尔。72,2132-2140)和昆津病毒亚基因组复制子(Khromykh，A.A.，Westaway，例如，1997)。昆津黄病毒亚基因组复制子的构建及应用。J.维罗尔。71、1497-1505)改变了突变体的感染性，降低了RNA复制的效率。这里，将这些缺失叠加到我们先前构建的二级结构模型上，并模拟了修改后的3‘-UTR序列的折叠。分析表明，大多数缺失破坏或重塑了二级结构的保守元件，这些缺失的生物学效应可能是3‘-UTR的结构重排，而不是序列基序的丢失。分析还表明，黄病毒3‘-UTR的整体结构完整性对于其启动子功能的最佳发挥至关重要，尽管可以定义两个不同的部分：最接近的结构和序列，可能是启动负链RNA合成的关键，以及更近端的结构和序列，可能作为病毒RNA复制的增强剂。还讨论了某些结构元件的功能意义以及它们对病毒在不同细胞中复制效率的可能影响。(C)1999 Elsevier Science B.V.保留所有权利。
It was previously reported that deletions introduced into the 3'-untranslated region (3'-UTR) of dengue type 4 (DEN 4) virus (Men, R., Bray, M., Clark, D., Chanock, R.M., Lai, C.J., 1996. DEN 4 virus mutants containing deletions in the 3'-noncoding region of the RNA genome: analysis of growth restriction in cell culture and altered viremia pattern and immunogenicity in Rhesus monkeys. J. Virol. 70, 3930-3937), tick-borne encephalitis (TBE) virus (Mandl, C.W., Holzmann, H., Meixner, T., Rauscher, S., Stadler, P.F., Allison, S.L., Heinz, F.X., 1998. Spontaneous and engineered deletions in the 3'-noncoding region of TBE virus: construction of highly attenuated mutants of a flavivirus. J. Virol. 72, 2132-2140) and subgenomic replicons of Kunjin virus (Khromykh, A.A., Westaway, E.G., 1997. Subgenomic replicons of the flavivirus Kunjin: construction and applications. J. Virol. 71, 1497-1505) altered the infectivity of the mutants and reduced the efficiency of RNA replication. Here, these deletions were superimposed onto the models of secondary structure we constructed previously and the folding of the modified 3'-UTR sequences was simulated. The analysis showed that most of the deletions disrupted or reshaped conserved elements of secondary structure and that the biological effects of these deletions are likely to represent structural rearrangements in the 3'-UTR, rather than the loss of sequence motifs. The analysis also suggested that the overall structural integrity of the flaviviral 3'-UTR is essential for optimal performance of its promotor function, although two distinct parts can be defined: the most 3'-terminal structures and sequences which may be critical for the initiation of minus-strand RNA synthesis, and more proximal structures and sequences that possibly function as enhancers of viral RNA replication. The functional significance of certain structural elements and their possible effect on the efficiency of viral replication in different cells are also discussed. (C) 1999 Elsevier Science B.V. All rights reserved.