在呼吸道RNA病毒基因组中,短暂RNA结构-RNA聚合酶相互作用的演变
Charlotte V Rigby1,2,3, Kimberly R Sabsay1,4, Karishma Bisht1
1Lewis Thomas Laboratory, Department of Molecular Biology, Princeton University, Washington Road, Princeton, NJ 08544, USA.
Virus evolution
|September 11, 2023
概括
新兴的RNA病毒如流感和冠状病毒通过减少RNA基因组的自由能量来适应人类. 这种RNA结构变化,特别是在模板循环中,可能会增强病毒复制和在新宿主中传播.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 基因组学就是基因组学.
背景情况:
- RNA病毒,包括A型流感病毒 (IAV) 和冠状病毒 (CoV),作为引起流行病和大流行病的人类病原体,构成重大威胁.
- 病毒适应人类宿主包括逃避免疫反应,优化复制和传播,影响病毒蛋白质和RNA结构.
- 病毒基因组内的RNA结构,如模板循环 (t-loop),影响病毒RNA合成,基因组包装和宿主免疫激活.
研究的目的:
- 调查在流行和新兴流感A病毒的人类适应期间RNA模板循环结构的变化.
- 确定RNA自由能量的变化是否有助于呼吸道RNA病毒适应人类群体.
主要方法:
- 基于细胞培养的复制试验被用于研究病毒适应.
- 进行了in silico序列分析,以评估RNA结构和自由能量.
- 对不同流感病毒株 (H3N2,H1N1,流感B) 和SARS-CoV-2分离物进行了RNA结构的比较分析.
主要成果:
- 从1968年到2017年,IAV H3N2 RNA聚合酶对t-循环的敏感性增加,伴随着t-循环自由能量减少,特别是在PB1基因中.
- H1N1 IAV在t-循环自由能量中表现出两种明显的减少,1918年后和2009年后的流行病.
- 虽然B型流感病毒没有表现出t环不稳定,但SARS-CoV-2的分离物显示出不稳定的病毒RNA结构.
结论:
- 减少RNA结构的自由能量,特别是t-循环,是新出现的呼吸道RNA病毒适应人类宿主的一个潜在机制.
- 这种基因组不稳定可能有助于增强病毒复制和在人类人口中传播.
- 这些发现表明,在不同的新兴呼吸道RNA病毒中,存在一种保存的适应性策略.
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