The role of RNA folding free energy in the evolution of the polymerase genes of the influenza A virus.
The role of RNA folding free energy in the evolution of the polymerase genes of the influenza A virus.
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DOI：
10.1186/gb-2009-10-2-r18
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发表时间：
2009-02-12
期刊：
影响因子：
12.3
通讯作者：
Benos PV
中科院分区：
文献类型：
--
作者：
Brower-Sinning R;Carter DM;Crevar CJ;Ghedin E;Ross TM;Benos PV
RNA折叠自由能对于流感病毒的进化和宿主适应是重要的。人类病毒聚合酶基因显示出比它们的禽类对应物具有显著更高的折叠自由能值。甲型流感病毒基因组由8个负极性的单链RNA片段组成。虽然已知血凝素和神经氨酸酶基因在宿主适应中起关键作用，但聚合酶基因（其编码聚合酶片段PB 2、PB 1、PA）和核蛋白基因对于病毒在宿主中的有效繁殖及其适应新宿主也是重要的。目前，了解病毒宿主特异性的努力主要集中在禽流感和人类分离株之间的氨基酸差异上。在这里，我们表明，RNA片段的折叠自由能可能在流感病毒的进化和宿主适应中发挥同样重要的作用。折叠自由能可以影响病毒RNA的稳定性，并影响病毒蛋白质翻译的速率。我们发现，有一个明确的区别之间的禽流感和人类的折叠自由能分布的聚合酶和核蛋白基因，与人类病毒具有显着更高的折叠自由能值。这种差异与氨基酸组成和密码子偏好无关。此外，通常传播的人类病毒的折叠自由能值在它们进入人类群体后的多年中倾向于向更高的值转变。最后，我们的研究结果表明，细胞生长的温度影响感染效率。我们的数据首次表明，RNA结构稳定性可能在甲型流感病毒的出现和宿主转移中起重要作用。细胞温度会影响病毒在哺乳动物细胞中的繁殖，这一事实可能有助于识别那些对人类构成更高威胁的鸟类毒株。
RNA folding free energy is important for the evolution and host-adaptation of the influenza virus. Human virus polymerase genes are shown to have substantially higher folding free energy values than their avian counterparts. The influenza A virus genome is composed of eight single-stranded RNA segments of negative polarity. Although the hemagglutinin and neuraminidase genes are known to play a key role in host adaptation, the polymerase genes (which encode the polymerase segments PB2, PB1, PA) and the nucleoprotein gene are also important for the efficient propagation of the virus in the host and for its adaptation to new hosts. Current efforts to understand the host-specificity of the virus have largely focused on the amino acid differences between avian and human isolates. Here we show that the folding free energy of the RNA segments may play an equally important role in the evolution and host adaptation of the influenza virus. Folding free energy may affect the stability of the viral RNA and influence the rate of viral protein translation. We found that there is a clear distinction between the avian and human folding free energy distributions for the polymerase and the nucleoprotein genes, with human viruses having substantially higher folding free energy values. This difference is independent of the amino acid composition and the codon bias. Furthermore, the folding free energy values of the commonly circulating human viruses tend to shift towards higher values over the years, after they entered the human population. Finally, our results indicate that the temperature in which the cells grow affects infection efficiency. Our data suggest for the first time that RNA structure stability may play an important role in the emergence and host shift of influenza A virus. The fact that cell temperature affects virus propagation in mammalian cells could help identify those avian strains that pose a higher threat to humans.
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影响因子：
5.4
作者：
Marsh, Glenn A.;Rabadan, Raul;Palese, Peter
通讯作者：
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DOI：
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发表时间：
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