A Conserved Secondary Structural Element in the Coding Region of the Influenza A Virus Nucleoprotein (NP) mRNA Is Important for the Regulation of Viral Proliferation.
A Conserved Secondary Structural Element in the Coding Region of the Influenza A Virus Nucleoprotein (NP) mRNA Is Important for the Regulation of Viral Proliferation.
复制标题
DOI：
10.1371/journal.pone.0141132
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Kierzek E
中科院分区：
文献类型：
--
作者：
Soszynska-Jozwiak M;Michalak P;Moss WN;Kierzek R;Kierzek E
甲型流感病毒是对人类的威胁，由于季节性流行病和罕见的，但危险的，导致广泛感染和死亡的流行病。八个RNA片段构成该病毒的基因组，并且它们通过从基因组（-）RNA模板链产生的编码（+）RNA的选择性剪接编码多于八种蛋白质。RNA在其生命周期中至关重要。对编码核蛋白的片段5进行生物信息学分析，发现（+）RNA中存在保守的结构基序。通过能量最小化和比较分析提出的二级结构与基于实验数据预测的结构一致，所述实验数据使用包含甲型流感病毒共有序列以及完整片段5（+）RNA（毒株A/VietNam/1203/2004（H5 N1））的121个核苷酸体外RNA构建体。保守的基序由三个发夹结构组成，其中一个在热力学上特别稳定。在细胞系中使用反义寡核苷酸的实验中支持这种保守的二级结构的生物学重要性，该实验发现这种基序的破坏导致病毒适应性的抑制。这些结果表明，在片段5（+）RNA的保守基序可能是一个候选人的抗病毒治疗为基础的阿托伐他汀。
Influenza A virus is a threat to humans due to seasonal epidemics and infrequent, but dangerous, pandemics that lead to widespread infection and death. Eight segments of RNA constitute the genome of this virus and they encode greater than eight proteins via alternative splicing of coding (+)RNAs generated from the genomic (-)RNA template strand. RNA is essential in its life cycle. A bioinformatics analysis of segment 5, which encodes nucleoprotein, revealed a conserved structural motif in the (+)RNA. The secondary structure proposed by energy minimization and comparative analysis agrees with structure predicted based on experimental data using a 121 nucleotide in vitro RNA construct comprising an influenza A virus consensus sequence and also an entire segment 5 (+)RNA (strain A/VietNam/1203/2004 (H5N1)). The conserved motif consists of three hairpins with one being especially thermodynamically stable. The biological importance of this conserved secondary structure is supported in experiments using antisense oligonucleotides in cell line, which found that disruption of this motif led to inhibition of viral fitness. These results suggest that this conserved motif in the segment 5 (+)RNA might be a candidate for oligonucleotide-based antiviral therapy.