An RNA conformational shift in recent H5N1 influenza A viruses
An RNA conformational shift in recent H5N1 influenza A viruses
复制标题
DOI：
10.1093/bioinformatics/btl559
复制
发表时间：
2007-02-01
期刊：
影响因子：
5.8
通讯作者：
Olsthoorn, Rene C. L.
中科院分区：
文献类型：
--
作者：
Gultyaev, Alexander P.;Heus, Hans A.;Olsthoorn, Rene C. L.
最近爆发的禽流感是由毒性异常的H5N1毒株引起的。目前还不清楚是什么使这些最近的H5N1毒株比以前流行的毒株更具侵略性。在这里，我们比较了3000多个A型流感病毒片段8的RNA序列，发现了一个独特的单核苷酸取代，通常与最近的H5N1毒株相关。通过系统发育分析、生物化学和生物物理学实验，我们证明了这种替换显著影响了NS基因3'剪接位点附近发夹和假结构象之间的平衡。这种构象转变可能对片段8 mRNA的剪接调控产生影响。我们的数据表明，除了蛋白质水平的变化，RNA二级结构的变化应认真考虑试图解释流感病毒的进化。
Recent outbreaks of avian influenza are being caused by unusually virulent H5N1 strains. It is unknown what makes these recent H5N1 strains more aggressive than previously circulating strains. Here, we have compared more than 3000 RNA sequences of segment 8 of type A influenza viruses and found a unique single nucleotide substitution typically associated with recent H5N1 strains. By phylogenetic analysis, biochemical and biophysical experiments, we demonstrate that this substitution dramatically affects the equilibrium between a hairpin and a pseudoknot conformation near the 3' splice-site of the NS gene. This conformational shift may have consequences for splicing regulation of segment 8 mRNA. Our data suggest that besides changes at the protein level, changes in RNA secondary structure should be seriously considered when attempting to explain influenza virus evolution.