Viral reassortment as an information exchange between viral segments
Viral reassortment as an information exchange between viral segments
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DOI：
10.1073/pnas.1113300109
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发表时间：
2012-02-28
影响因子：
11.1
通讯作者：
Rabadan, Raul
中科院分区：
文献类型：
--
作者：
Greenbaum, Benjamin D.;Li, Olive T. W.;Rabadan, Raul
病毒具有非凡的多样化和进化能力。对于分节段病毒，重配可以通过允许共感染菌株之间的遗传物质的直接交换来引入剧烈的基因组和表型变化。例如，多个流感大流行是由通常在不同宿主中发现的病毒的再感染引起的。然而，目前尚不清楚的是驱动这些事件的潜在机制，以及共同感染产生的菌株多样性的内在偏倚水平。为了解决这个问题，以前的实验寻找体外共感染细胞的菌株片段之间的相关性。在这里，我们提出了一个信息理论的方法作为这个问题的自然数学框架。我们研究了流感病毒和其他分段病毒，病毒的片段在多大程度上可以跨感染和相互之间传递菌株信息。我们的方法超越了以前的关联研究，量化了新出现的菌株的多样性被重配模式改变了多少，在多个菌株和细胞类型之间是否存在一致的偏差，以及是否在两个以上的片段之间共享重要信息。我们将我们的方法应用到一个新的实验中，该实验研究了2009年H1N1大流行和季节性H1N1毒株之间的重配模式，通过与先前报道的毒株重组进行比较，将其片段信息共享置于背景中。我们发现跨类实验和以前未观察到的更高层次的结构的进化模式。最后，我们展示了如何将这种方法与毒力潜力相结合，以评估大流行的威胁。
Viruses have an extraordinary ability to diversify and evolve. For segmented viruses, reassortment can introduce drastic genomic and phenotypic changes by allowing a direct exchange of genetic material between coinfecting strains. For instance, multiple influenza pandemics were caused by reassortments of viruses typically found in separate hosts. What is unclear, however, are the underlying mechanisms driving these events and the level of intrinsic bias in the diversity of strains that emerge from coinfection. To address this problem, previous experiments looked for correlations between segments of strains that coinfect cells in vitro. Here, we present an information theory approach as the natural mathematical framework for this question. We study, for influenza and other segmented viruses, the extent to which a virus's segments can communicate strain information across an infection and among one another. Our approach goes beyond previous association studies and quantifies how much the diversity of emerging strains is altered by patterns in reassortment, whether biases are consistent across multiple strains and cell types, and if significant information is shared among more than two segments. We apply our approach to a new experiment that examines reassortment patterns between the 2009 H1N1 pandemic and seasonal H1N1 strains, contextualizing its segmental information sharing by comparison with previously reported strain reassortments. We find evolutionary patterns across classes of experiments and previously unobserved higher-level structures. Finally, we show how this approach can be combined with virulence potentials to assess pandemic threats.